Skip to main content

Articular Cartilage: Homeostasis, Aging and Degeneration

  • Chapter
  • First Online:
Book cover Articular Cartilage of the Knee

Abstract

Aging implies changes in articular cartilage cells and the surrounding extracellular matrix (ECM) that are reflective of metabolic changes related to time alone. For chondrocytes, these are genomic and intracytoplasmic changes that lessen their capacity to respond and control their extracellular environment; for the matrix, these are changes that lead to decreased hydration and increased brittleness of the tissue. Clinically, this can manifest as decreased capacity to withstand mechanical forces leading to degenerative arthritis.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Gahunia HK, Pritzker KP. Effect of exercise on articular cartilage. Orthop Clin North Am. 2012;43:187–99.

    Article  PubMed  Google Scholar 

  2. Makinejad MD, Abu Osman NA, Abu Bakar Wan Abas W, Bayat M. Preliminary analysis of knee stress in full extension landing. Clinics (Sao Paulo). 2013;68:1180–8.

    Google Scholar 

  3. Asanbaeva A, Masuda K, Thonar EJ, Klisch SM, Sah RL. Regulation of immature cartilage growth by IGF-I, TGF-β1, BMP-7, and PDGF-AB: role of metabolic balance between fixed charge and collagen network. Biomech Model Mechanobiol. 2008;7:263–76.

    Google Scholar 

  4. Murphy CL, Sambanis A. Effect of oxygen tension on chondrocyte extracellular matrix accumulation. Connect Tissue Res. 2001;42:87–96.

    Article  CAS  PubMed  Google Scholar 

  5. Fermor B, Christensen SE, Youn I, Cernanec JM, Davies CM, Weinberg JB. Oxygen, nitric oxide and articular cartilage. Eur Cell Mater. 2007;13:56–65.

    Article  CAS  PubMed  Google Scholar 

  6. Schrobback K, Malda J, Crawford RW, Upton Z, Leavesley DI, Klein TJ. Effects of oxygen on zonal marker expression in human articular chondrocytes. Tissue Eng Part A. 2012;18:920–33.

    Article  CAS  PubMed  Google Scholar 

  7. Mobasheri A, Richardson S, Mobasheri R, Shakibaei M, Hoyland JA. Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes. Histol Histopathol. 2005;20:1327–38.

    CAS  PubMed  Google Scholar 

  8. Pfander D, Gelse K. Hypoxia and osteoarthritis: how chondrocytes survive hypoxic environments. Curr Opin Rheumatol. 2007;19:457–62.

    Article  CAS  PubMed  Google Scholar 

  9. Goldring MB, Marcu KB. Cartilage homeostasis in health and rheumatic diseases. Arthritis Res Ther. 2009;11:224.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Guilak F, Jones WR, Ting-Beall HP, Lee GM. The deformation behavior and mechanical properties of chondrocytes in articular cartilage. Osteoarthritis Cartilage. 1999;7:59–70.

    Article  CAS  PubMed  Google Scholar 

  11. Knight MM, Ross JM, Sherwin AF, Lee DA, Bader DL, Poole CA. Chondrocyte deformation within mechanically and enzymatically extracted chondrons compressed in agarose. Biochim Biophys Acta. 2001;1526:141–6.

    Article  CAS  PubMed  Google Scholar 

  12. Chen SS, Falcovitz YH, Schneiderman R, Maroudas A, Sah RL. Depth-dependent compressive properties of normal aged human femoral head articular cartilage: relationship to fixed charge density. Osteoarthritis Cartilage. 2001;9:561–9.

    Article  CAS  PubMed  Google Scholar 

  13. Maroudas A, Bullough P, Swanson SA, Freeman MA. The permeability of articular cartilage. J Bone Joint Surg Br. 1968;50:166–77.

    Google Scholar 

  14. Cawston TE, Wilson AJ. Understanding the role of tissue degrading enzymes and their inhibitors in development and disease. Best Pract Res Clin Rheumatol. 2006;20:983–1002.

    Article  CAS  PubMed  Google Scholar 

  15. Dancevic CM, McCulloch DR. Current and emerging therapeutic strategies for preventing inflammation and aggrecanase-mediated cartilage destruction in arthritis. Arthritis Res Ther. 2014;16:429.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Martin JA, Brown TD, Heiner AD, Buckwalter JA. Chondrocyte senescence, joint loading and osteoarthritis. Clin Orthop Relat Res. 2004;427:S96–103.

    Article  Google Scholar 

  17. Poole CA. Articular cartilage chondrons: form, function and failure. J Anat. 1997;191(Pt 1):1–13.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Poole CA, Flint MH, Beaumont BW. Chondrons in cartilage: ultrastructural analysis of the pericellular microenvironment in adult human articular cartilages. J Orthop Res. 1987;5:509–22.

    Article  CAS  PubMed  Google Scholar 

  19. Chang J, Poole CA. Sequestration of type VI collagen in the pericellular microenvironment of adult chondrocytes cultured in agarose. Osteoarthritis Cartilage. 1996;4:275–85.

    Article  CAS  PubMed  Google Scholar 

  20. Poole CA, Wotton SF, Duance VC. Localization of type IX collagen in chondrons isolated from porcine articular cartilage and rat chondrosarcoma. Histochem J. 1988;20:567–74.

    Article  CAS  PubMed  Google Scholar 

  21. von der Mark K, Kirsch T, Nerlich A, Kuss A, Weseloh G, Gluckert K, Stoss H. Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy. Arthritis Rheum. 1992;35:806–11.

    Article  PubMed  Google Scholar 

  22. Wilusz RE, Sanchez-Adams J, Guilak F. The structure and function of the pericellular matrix of articular cartilage. Matrix Biol. 2014;39:25–32.

    Article  CAS  PubMed  Google Scholar 

  23. Zhang Z. Chondrons and the pericellular matrix of chondrocytes. Tissue Eng Part B Rev. 2015;21:267–77.

    Article  PubMed  Google Scholar 

  24. Vonk LA, de Windt TS, Kragten AH, Beekhuizen M, Mastbergen SC, Dhert WJ, Lafeber FP, Creemers LB, Saris DB. Enhanced cell-induced articular cartilage regeneration by chondrons; the influence of joint damage and harvest site. Osteoarthritis Cartilage. 2014;22:1910–7.

    Article  CAS  PubMed  Google Scholar 

  25. Guo H, Torzilli PA. Shape of chondrocytes within articular cartilage affects the solid but not the fluid microenvironment under unconfined compression. Acta Biomater. 2016;29:170–9.

    Article  CAS  PubMed  Google Scholar 

  26. Verzijl N, DeGroot J, Thorpe SR, Bank RA, Shaw JN, Lyons TJ, Bijlsma JW, Lafeber FP, Baynes JW, TeKoppele JM. Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem. 2000;275(50):39027–31.

    Article  CAS  PubMed  Google Scholar 

  27. Maroudas A, Palla G, Gilav E. Racemization of aspartic acid in human articular cartilage. Connect Tissue Res. 1992;28(3):161–9.

    Article  CAS  PubMed  Google Scholar 

  28. Kempson GE. Relationship between the tensile properties of articular cartilage from the human knee and age. Ann Rheum Dis. 1982;41:508–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kempson GE. Mechanical properties of articular cartilage and their relationship to matrix degradation and age. Ann Rheum Dis. 1975;34(Suppl 2):111–3.

    Google Scholar 

  30. Kempson GE. Mechanical properties of articular cartilage. J Physiol. 1972;223:23P.

    CAS  PubMed  Google Scholar 

  31. Klein TJ, Chaudhry M, Bae WC, Sah RL. Depth-dependent biomechanical and biochemical properties of fetal, newborn, and tissue-engineered articular cartilage. J Biomech. 2007;40:182–90.

    Article  PubMed  Google Scholar 

  32. Chan EF, Harjanto R, Asahara H, Inoue N, Masuda K, Bugbee WD, Firestein GS, Hosalkar HS, Lotz MK, Sah RL. Structural and functional maturation of distal femoral cartilage and bone during postnatal development and growth in humans and mice. Orthop Clin North Am. 2012;43:173–85.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Asanbaeva A, Tam J, Schumacher BL, Klisch SM, Masuda K, Sah RL. Articular cartilage tensile integrity: modulation by matrix depletion is maturation-dependent. Arch Biochem Biophys. 2008;474:175–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Li LP, Cheung JT, Herzog W. Three-dimensional fibril-reinforced finite element model of articular cartilage. Med Biol Eng Comput. 2009;47:607–15.

    Article  CAS  PubMed  Google Scholar 

  35. Roth V, Mow VC. The intrinsic tensile behavior of the matrix of bovine articular cartilage and its variation with age. J Bone Joint Surg Am. 1980;62:1102–17.

    Article  CAS  PubMed  Google Scholar 

  36. Kempson GE, Spivey CJ, Swanson SA, Freeman MA. Patterns of cartilage stiffness on normal and degenerate human femoral heads. J Biomech. 1971;4:597–609.

    Article  CAS  PubMed  Google Scholar 

  37. Kempson GE, Freeman MA, Swanson SA. Tensile properties of articular cartilage. Nature. 1968;220:1127–8.

    Article  CAS  PubMed  Google Scholar 

  38. Gottardi R, Hansen U, Raiteri R, Loparic M, Düggelin M, Mathys D, Friederich NF, Bruckner P, Stolz M. Supramolecular organization of collagen fibrils in healthy and osteoarthritic human knee and hip joint cartilage. PLoS One. 2016;11:e0163552.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Han EH, Chen SS, Klisch SM, Sah RL. Contribution of proteoglycan osmotic swelling pressure to the compressive properties of articular cartilage. Biophys J. 2011;101:916–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Broom ND. Further insights into the structural principles governing the function of articular cartilage. J Anat. 1984;139(Pt 2):275–94.

    PubMed  PubMed Central  Google Scholar 

  41. Eleswarapu SV, Responte DJ, Athanasiou KA. Tensile properties, collagen content, and crosslinks in connective tissues of the immature knee joint. PLoS One. 2011;6:e26178.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Williamson AK, Chen AC, Masuda K, Thonar EJ, Sah RL. Tensile mechanical properties of bovine articular cartilage: variations with growth and relationships to collagen network components. J Orthop Res. 2003;21:872–80.

    Article  CAS  PubMed  Google Scholar 

  43. Loeser RF. Molecular mechanisms of cartilage destruction: mechanics, inflammatory mediators, and aging collide. Arthritis Rheum. 2006;54:1357–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Dudhia J. Aggrecan, aging and assembly in articular cartilage. Cell Mol Life Sci. 2005;62:2241–56.

    Article  CAS  PubMed  Google Scholar 

  45. Aigner T, Haag J, Martin J, Buckwalter J. Osteoarthritis: aging of matrix and cells--going for a remedy. Curr Drug Targets. 2007;8:325–31.

    Article  CAS  PubMed  Google Scholar 

  46. Verzijl N, Bank RA, TeKoppele JM, DeGroot J. AGEing and osteoarthritis: a different perspective. Curr Opin Rheumatol. 2003;15:616–22.

    Article  PubMed  Google Scholar 

  47. Yang L, Carlson SG, McBurney D, Horton WE Jr. Multiple signals induce endoplasmic reticulum stress in both primary and immortalized chondrocytes resulting in loss of differentiation, impaired cell growth, and apoptosis. J Biol Chem. 2005;280:31156–65.

    Article  CAS  PubMed  Google Scholar 

  48. Grogan SP, D’Lima DD. Joint aging and chondrocyte cell death. Int J Clin Rheumatol. 2010;5:199–214.

    Article  Google Scholar 

  49. Minguzzi M, Cetrullo S, D’Adamo S, Silvestri Y, Flamigni F, Borzì RM. Emerging players at the intersection of chondrocyte loss of maturational arrest, oxidative stress, senescence and low-grade inflammation in osteoarthritis. Oxid Med Cell Longev. 2018;2018:3075293. doi: 10.1155/2018/3075293.

    Google Scholar 

  50. Jeon OH, David N, Campisi J, Elisseeff JH. Senescent cells and osteoarthritis: a painful connection. J Clin Invest. 2018;128(4):1229–37.

    Google Scholar 

  51. Blanco FJ, Guitian R, Vazquez-Martul E, de Toro FJ, Galdo F. Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology. Arthritis Rheum. 1998;41:284–9.

    Article  CAS  PubMed  Google Scholar 

  52. Aigner T, Hemmel M, Neureiter D, Gebhard PM, Zeiler G, Kirchner T, McKenna L. Apoptotic cell death is not a widespread phenomenon in normal aging and osteoarthritis human articular knee cartilage: a study of proliferation, programmed cell death (apoptosis), and viability of chondrocytes in normal and osteoarthritic human knee cartilage. Arthritis Rheum. 2001;44:1304–12.

    Article  CAS  PubMed  Google Scholar 

  53. Chang J, Wang W, Zhang H, Hu Y, Wang M, Yin Z. The dual role of autophagy in chondrocyte responses in the pathogenesis of articular cartilage degeneration in osteoarthritis. Int J Mol Med. 2013;32:1311–8.

    Article  CAS  PubMed  Google Scholar 

  54. Carames B, Taniguchi N, Otsuki S, Blanco FJ, Lotz M. Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis. Arthritis Rheum. 2010;62:791–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Carames B, Olmer M, Kiosses WB, Lotz MK. The relationship of autophagy defects to cartilage damage during joint aging in a mouse model. Arthritis Rheum. 2015;67:1568–76.

    Article  CAS  Google Scholar 

  56. Martin JA, Buckwalter JA. Roles of articular cartilage aging and chondrocyte senescence in the pathogenesis of osteoarthritis. Iowa Orthop J. 2001;21:1–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Ma CH, Wu CH, Jou IM, Tu YK, Hung CH, et al. PKR promotes oxidative stress and apoptosis of human articular chondrocytes by causing mitochondrial dysfunction through p38 MAPK activation-PKR activation causes apoptosis in human chondrocytes. Antioxidants (Basel). 2019;8(9):E370. doi: 10.3390/antiox8090370.

    Google Scholar 

  58. Martin JA, Buckwalter JA. Telomere erosion and senescence in human articular cartilage chondrocytes. J Gerontol A Biol Sci Med Sci. 2001;56A:B172–9.

    Article  CAS  Google Scholar 

  59. Martin JA, Buckwalter JA. Aging, articular cartilage chondrocyte senescence and osteoarthritis. Biogerontology. 2002;3:257–64.

    Article  CAS  PubMed  Google Scholar 

  60. Martin JA, Klingelhutz AJ, Moussavi-Harami F, Buckwalter JA. Effects of oxidative damage and telomerase activity on human articular cartilage chondrocyte senescence. J Gerontol Ser A Biol Sci Med Sci. 2004;59:324–37.

    Article  Google Scholar 

  61. Loeser RF. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthritis Cartilage. 2009;17:971–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Harbo M, Delaisse JM, Kjaersgaard-Andersen P, Soerensen FB, Koelvraa S, Bendix L. The relationship between ultra-short telomeres, aging of articular cartilage and the development of human hip osteoarthritis. Mech Ageing Dev. 2013;134:367–72.

    Article  CAS  PubMed  Google Scholar 

  63. Leong DJ, Sun HB. Events in articular chondrocytes with aging. Curr Osteoporos Rep. 2011;9:196–201.

    Article  PubMed  Google Scholar 

  64. Jallali N, Ridha H, Thrasivoulou C, Underwood C, Butler PE, Cowen T. Vulnerability to ROS-induced cell death in ageing articular cartilage: the role of antioxidant enzyme activity. Osteoarthritis Cartilage. 2005;13:614–22.

    Article  CAS  PubMed  Google Scholar 

  65. Bates EJ, Harper GS, Lowther DA, Preston BN. Effect of oxygen-derived reactive species on cartilage proteoglycan-hyaluronate aggregates. Biochem Int. 1984;8:629–37.

    CAS  PubMed  Google Scholar 

  66. Bolduc JA, Collins JA, Loeser RF. Reactive oxygen species, aging and articular cartilage homeostasis. Free Radic Biol Med. 2019;132:73–82.

    Google Scholar 

  67. Krajewska-Włodarczyk M, Owczarczyk-Saczonek A, Placek W, Osowski A, Wojtkiewicz J. Articular cartilage aging-potential regenerative capacities of cell manipulation and stem cell therapy. Int J Mol Sci. 2018;19(2):E623.

    Google Scholar 

  68. Trelstad RL, Kang AH, Igarashi S, Gross J. Isolation of two distinct collagens from chick cartilage. Biochemistry. 1970;9:4993–8.

    Article  CAS  PubMed  Google Scholar 

  69. Mayne R. Cartilage collagens. What is their function and are they are involved in articular disease? Arthritis Rheum. 1989;32:241–6.

    Article  CAS  PubMed  Google Scholar 

  70. Benninghof A. Form und Bau der Gelenkknorpel in ihren Beziehungen zur Function. II. Der Aufbau des Gelenkknorpels in seinen Beziehungen zur Function. Z Zellforsch Mikrosk Anat. 1925;2:783–862.

    Article  Google Scholar 

  71. Speer DP, Dahners L. The collagenous architecture of articular cartilage. Clin Orthop Relat Res. 1979;139:267–75.

    Google Scholar 

  72. Hwang WS, Li B, Jin LH, Ngo K, Schachar NS, Hughes GNF. Collagen fibril structure of normal aging, and osteoarthritic cartilage. J Pathol. 1992;167:425–33.

    Article  CAS  PubMed  Google Scholar 

  73. Lotz M, Loeser RF. Effects of aging on articular cartilage homeostasis. Bone. 2012;51:241–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Rieppo L, Saarakkala S, Narhi T, Holopainen J, Lammi M, Helminen HJ, Jurvelin JS, Rieppo J. Quantitative analysis of spatial proteoglycan content in articular cartilage with Fourier transform infrared imaging spectroscopy: critical evaluation of analysis methods and specificity of the parameters. Microsc Res Tech. 2010;73:503–12.

    CAS  PubMed  Google Scholar 

  75. Yin J, Xia Y, Lu M. Concentration profiles of collagen and proteoglycan in articular cartilage by Fourier transform infrared imaging and principal component regression. Spectrochim Acta Mol Biomol Spectrosc. 2012;88:90–6.

    Google Scholar 

  76. Paul PK, O’Byrne E, Blancuzzi V, Wilson D, Gunson D, Douglas FL, Wang JZ, Mezrich RS. Magnetic resonance imaging reflects cartilage proteoglycan degradation in the rabbit knee. Skelet Radiol. 1991;20:31–6.

    Article  CAS  Google Scholar 

  77. Wang Q, Zheng YP, Niu HJ. Changes in triphasic mechanical properties of proteoglycan-depleted articular cartilage extracted from osmotic swelling behavior monitored using high-frequency ultrasound. Mol Cell Biomech. 2010;7:45–58.

    CAS  PubMed  Google Scholar 

  78. Inerot S, Heinegard D, Audell L, Olsson SE. Articular-cartilage proteoglycans in aging and osteoarthritis. Biochem J. 1978;169:143–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Lauder RM, Huckerby TN, Nieduszynski IA, Plaas AH. Age-related changes in the structure of the keratan sulphate chains attached to fibromodulin isolated from articular cartilage. Biochem J. 1998;330(Pt 2):753–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Theocharis DA, Kalpaxis DL, Tsiganos CP. Cartilage keratan sulphate: changes in chain length with ageing. Biochim Biophys Acta. 1985;841:131–4.

    Article  CAS  PubMed  Google Scholar 

  81. Hopwood JJ, Robinson HC. The structure and composition of cartilage keratan sulphate. Biochem J. 1974;141:517–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Thambyah A, Zhao JY, Bevill SL, Broom ND. Macro-, micro- and ultrastructural investigation of how degeneration influences the response of cartilage to loading. J Mech Behav Biomed Mater. 2012;5:206–15.

    Article  CAS  PubMed  Google Scholar 

  83. Kwiecinski JJ, Dorosz SG, Ludwig TE, Abubacker S, Cowman MK, Schmidt TA. The effect of molecular weight on hyaluronan’s cartilage boundary lubricating ability – alone and in combination with proteoglycan 4. Osteoarthritis Cartilage. 2011;19:1356–62.

    Google Scholar 

  84. Abubacker S, Ham HO, Messersmith PB, Schmidt TA. Cartilage boundary lubricating ability of aldehyde modified proteoglycan 4 (PRG4-CHO). Osteoarthritis Cartilage. 2013;21:186–9.

    Article  CAS  PubMed  Google Scholar 

  85. Oloyede A, Gudimetla P, Chen Y, Crawford R. In vitro reversal of the load-bearing properties of lipid-depleted articular cartilage following exposure to phospholipid surfactant solutions. Clin Biomech (Bristol, Avon). 2008;23:1200–8.

    Article  CAS  Google Scholar 

  86. Chang DP, Guilak F, Jay GD, Zauscher S. Interaction of lubricin with type II collagen surfaces: adsorption, friction, and normal forces. J Biomech. 2014;47:659–66.

    Article  PubMed  Google Scholar 

  87. Ghadially FN, Meachim G, Collins DH. Extra-cellular lipid in the matrix of human articular cartilage. Ann Rheum Dis. 1965;24:136–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Stockwell RA. Lipid in the matrix of ageing articular cartilage. Nature. 1965;207:427–8.

    Article  CAS  PubMed  Google Scholar 

  89. Rabinowitz JL, Gregg JR, Nixon JE, Schumacher HR. Lipid composition of the tissues of human knee joints. I. Observations in normal joints (articular cartilage, meniscus, ligaments, synovial fluid, synovium, intra-articular fat pad and bone marrow). Clin Orthop Relat Res. 1979;(143):260–5.

    Google Scholar 

  90. Schmidt TA, Gastelum NS, Nguyen QT, Schumacher BL, Sah RL. Boundary lubrication of articular cartilage: role of synovial fluid constituents. Arthritis Rheum. 2007;56:882–91.

    Article  CAS  PubMed  Google Scholar 

  91. Sivan S, Schroeder A, Verberne G, Merkher Y, Diminsky D, Priev A, Maroudas A, Halperin G, Nitzan D, Etsion I, Barenholz Y. Liposomes act as effective biolubricants for friction reduction in human synovial joints. Langmuir. 2010;26:1107–16.

    Article  CAS  PubMed  Google Scholar 

  92. Mitrovic DR, Uzan M, Quintero M, Ryckewaert A. Lipid peroxides in human articular cartilage. Rheumatol Int. 1984;5:33–7.

    Article  CAS  PubMed  Google Scholar 

  93. Tiku ML, Shah R, Allison GT. Evidence linking chondrocyte lipid peroxidation to cartilage matrix protein degradation. Possible role in cartilage aging and the pathogenesis of osteoarthritis. J Biol Chem. 2000;275:20069–76.

    Article  CAS  PubMed  Google Scholar 

  94. Van Der Korst JK, Sokoloff L, Miller EJ. Senescent pigmentation of cartilage and degenerative joint disease. Arch Pathol. 1968;86:40–7.

    PubMed  Google Scholar 

  95. Tsukahara Y, Nasu T. Ceroid-like pigment in age changes of human cartilage. Acta Pathol Jpn. 1974;24:357–69.

    CAS  PubMed  Google Scholar 

  96. Van Der Korst JK, Willekens FL, Lansink AG, Henrichs AM. Age-associated glycopeptide pigment in human costal cartilage. Am J Pathol. 1977;89:605–19.

    PubMed  PubMed Central  Google Scholar 

  97. Rahmati M, Nalesso G, Mobasheri A, Mozafari M. Aging and osteoarthritis: central role of the extracellular matrix. Ageing Res Rev. 2017;40:20–30.

    Article  CAS  PubMed  Google Scholar 

  98. De Campos VB, Vilarta R. Articular cartilage: collagen II-proteoglycans interactions. Availability of reactive groups. Variation in birefringence and differences as compared to collagen I. Acta Histochem. 1988;83:189–205.

    Article  CAS  Google Scholar 

  99. Panula HE, Hyttinen MM, Arokoski JPA, Langsjo TK, Pelttari A, Kiviranta I, Helminen HJ. Articular cartilage superficial zone collagen birefringence reduced and cartilage thickness increased before surface fibrillation in experimental osteoarthritis. Ann Rheum Dis. 1998;57:237–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Verzijl N, DeGroot J, Oldehinkel E, Bank RA, Thorpe SR, Baynes JW, Bayliss MT, Bijlsma JW, Lafeber FP, Tekoppele JM. Age-related accumulation of Maillard reaction products in human articular cartilage collagen. Biochem J. 2000;350(Pt 2):381–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Monnier VM. Nonenzymatic glycosylation, the Maillard reaction and the aging process. J Gerontol. 1990;45:B105–11.

    Article  CAS  PubMed  Google Scholar 

  102. Graham L. A comprehensive survey of the acid-stable fluorescent cross-links formed by ribose with basic amino acids, and partial characterization of a novel Maillard cross-link. Biochim Biophys Acta. 1996;1297:9–16.

    Article  PubMed  Google Scholar 

  103. Pokharna HK, Pottenger LA. Nonenzymatic glycation of cartilage proteoglycans: an in vivo and in vitro study. Glycoconj J. 1997;14:917–23.

    Article  CAS  PubMed  Google Scholar 

  104. Uchiyama A, Ohishi T, Takahashi M, Kushida K, Inoue T, Fujie M, Horiuchi K. Fluorophores from aging human articular cartilage. J Biochem. 1991;110:714–8.

    Article  CAS  PubMed  Google Scholar 

  105. Sell DR, Monnier VM. End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen. J Clin Invest. 1990;85:380–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Bank RA, Bayliss MT, Lafeber FP, Maroudas A, Tekoppele JM. Ageing and zonal variation in post-translational modification of collagen in normal human articular cartilage. The age-related increase in non-enzymatic glycation affects biomechanical properties of cartilage. Biochem J. 1998;330(Pt 1):345–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Mow VC. In: Mow VC, Hayes WC, editors. Basic orthopedic biomechanics. 2nd ed. Philadelphia: Lippincott - Raven Press; 1997. p. 113–514.

    Google Scholar 

  108. Chen AC, Temple MM, Ng DM, Verzijl N, DeGroot J, TeKoppele JM, Sah RL. Induction of advanced glycation end products and alterations of the tensile properties of articular cartilage. Arthritis Rheum. 2002;46:3212–7.

    Article  CAS  PubMed  Google Scholar 

  109. Fick JM, Huttu MR, Lammi MJ, Korhonen RK. In vitro glycation of articular cartilage alters the biomechanical response of chondrocytes in a depth-dependent manner. Osteoarthritis Cartilage. 2014;22:1410–8.

    Article  CAS  PubMed  Google Scholar 

  110. DeGroot J, Verzijl N, Bank RA, Lafeber FP, Bijlsma JW, Tekoppele JM. Age-related decrease in proteoglycan synthesis of human articular chondrocytes: the role of nonenzymatic glycation. Arthritis Rheum. 1999;42:1003–9.

    Article  CAS  PubMed  Google Scholar 

  111. Hirose J, Yamabe S, Takada K, Okamoto N, Nagai R, Mizuta H. Immunohistochemical distribution of advanced glycation end products (AGEs) in human osteoarthritic cartilage. Acta Histochem. 2011;113:613–8.

    Article  CAS  PubMed  Google Scholar 

  112. Sessa L, Gatti E, Zeni F, Antonelli A, Catucci A, Koch M, Pompilio G, Fritz G, Raucci A, Bianchi ME. The receptor for advanced glycation end-products (RAGE) is only present in mammals, and belongs to a family of cell adhesion molecules (CAMs). PLoS One. 2014;9:e86903.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Dejica VM, Mort JS, Laverty S, Antoniou J, Zukor DJ, Tanzer M, Poole AR. Increased type II collagen cleavage by cathepsin K and collagenase activities with aging and osteoarthritis in human articular cartilage. Arthritis Res Ther. 2012;14:R113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Silver FH, Glasgold AI. Cartilage wound healing. An overview. Otolaryngol Clin N Am. 1995;28(5):847–64.

    CAS  Google Scholar 

  115. Gomoll AH, Minas T. The quality of healing: articular cartilage. Wound Repair Regen. 2014;22(Suppl 1):30–8.

    Article  PubMed  Google Scholar 

  116. Grynpas MD, Eyre DR, Kirschner DA. Collagen type II differs from type I in native molecular packing. Biochim Biophys Acta. 1980;626:346–55.

    Article  CAS  PubMed  Google Scholar 

  117. Chaminade F, Stanescu V, Stanescu R, Maroteaux P, Peyron JG. Noncollagenous proteins in cartilage of normal subjects and patients with degenerative joint disease. A gel electrophoretic study. Arthritis Rheum. 1982;25:1078–83.

    Article  CAS  PubMed  Google Scholar 

  118. Roughley PJ. Articular cartilage and changes in arthritis: noncollagenous proteins and proteoglycans in the extracellular matrix of cartilage. Arthritis Res. 2001;3:342–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Eisenstein R, Kuettner KE, Neapolitan C, Soble LW, Sorgente N. The resistance of certain tissues to invasion. III. Cartilage extracts inhibit the growth of fibroblasts and endothelial cells in culture. Am J Pathol. 1975;81:337–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Stanescu V, Do TP, Chaminade F, Maroteaux P, Stanescu R. Non-collagenous protein screening in the human chondrodysplasias: link proteins, cartilage oligomeric matrix protein (COMP), and fibromodulin. Am J Med Genet. 1994;51:22–8.

    Article  CAS  PubMed  Google Scholar 

  121. Neame PJ, Tapp H, Azizan A. Noncollagenous, nonproteoglycan macromolecules of cartilage. Cell Mol Life Sci. 1999;55:1327–40.

    Article  CAS  PubMed  Google Scholar 

  122. Bywaters EG, Dorling J. Amyloid deposits in articular cartilage. Ann Rheum Dis. 1970;29:294–306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Mohr W, Kuhn C, Linke RP, Wessinghage D. Deposition of amyloid of unknown origin in articular cartilage. Virchows Arch B Cell Pathol Incl Mol Pathol. 1991;60(4):259–62.

    Google Scholar 

  124. Athanasou NA, West L, Sallie B, Puddle B. Localized amyloid deposition in cartilage is glycosaminoglycans-associated. Histopathology. 1995;26:267–72.

    Article  CAS  PubMed  Google Scholar 

  125. Ladefoged C. Amyloid in osteoarthritic hip joints. A pathoanatomical and histological investigation of femoral head cartilage. Acta Orthop Scand. 1982;53:581–6.

    Article  CAS  PubMed  Google Scholar 

  126. Ladefoged C, Christensen HE, Sorensen KH. Amyloid in osteoarthritic hip joints. Depositions in cartilage and capsule. Semiquantitative aspects. Acta Orthop Scand. 1982;53:587–90.

    Article  CAS  PubMed  Google Scholar 

  127. Westermark P, Benson MD, Buxbaum JN, Cohen AS, Frangione B, Ikeda S, Masters CL, Merlini G, Saraiva MJ, Sipe JD. A primer of amyloid nomenclature. Amyloid. 2007;14:179–83.

    Article  CAS  PubMed  Google Scholar 

  128. Maroudas AI. Balance between swelling pressure and collagen tension in normal and degenerate cartilage. Nature. 1976;260:808–9.

    Article  CAS  PubMed  Google Scholar 

  129. Stockwell RA, Barnett CH. Changes in permeability of articular cartilage with age. Nature. 1964;201:835–6.

    Article  CAS  PubMed  Google Scholar 

  130. Kyriazis AP, Tsaltas TT. Studies in permeability of articular cartilage in New Zealand albino rabbits. The effect of aging, papain, and certain steroid hormones. Am J Pathol. 1971;62:75–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Duan W, Wei L, Zhang J, Hao Y, Li C, Li H, Li Q, Zhang Q, Chen W, Wei X. Alteration of viscoelastic properties is associated with a change in cytoskeleton components of ageing chondrocytes from rabbit knee articular cartilage. Mol Cell Biomech. 2011;8:253–74.

    PubMed  Google Scholar 

  132. Steklov N, Srivastava A, Sung KL, Chen PC, Lotz MK, D’Lima DD. Aging-related differences in chondrocyte viscoelastic properties. Mol Cell Biomech. 2009;6:113–9.

    PubMed  Google Scholar 

  133. Szarko M, Xia Y. Direct visualisation of the depth dependent mechanical properties of full-thickness articular cartilage. Open J Orthop. 2012; doi. 10.4236/ojo.2012.22007.

    Google Scholar 

  134. Chen C, Tambe DT, Deng L, Yang L. Biomechanical properties and mechanobiology of the articular chondrocyte. Am J Physiol Cell Physiol. 2013;305:C1202–8.

    Article  CAS  PubMed  Google Scholar 

  135. Peters AE, Akhtar R, Comerford EJ, Bates KT. The effect of ageing and osteoarthritis on the mechanical properties of cartilage and bone in the human knee joint. Sci Rep. 2018;8(1):5931.

    Google Scholar 

  136. Goldring MB, Goldring SR. Osteoarthritis. J Cell Physiol. 2007;213:626–34.

    Article  CAS  PubMed  Google Scholar 

  137. Houard X, Goldring MB, Berenbaum F. Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis. Curr Rheumatol Rep. 2013;15:375.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Loeser RF, Gandhi U, Long DL, Yin W, Chubinskaya S. Aging and oxidative stress reduce the response of human articular chondrocytes to insulin-like growth factor-1 and osteogenic protein-1. Arthritis Rheum. 2014;66:2201–9.

    Article  CAS  Google Scholar 

  139. van Caam A, Madej W, Thijssen E, Garcia de Vinuesa A, van den Berg W, Goumans MJ, Ten Dijke P, Blaney Davidson E, van der Kraan PM. Expression of TGFβ-family signalling components in ageing cartilage: age-related loss of TGFβ and BMP receptors. Osteoarthritis Cartilage. 2016;24:1235–45.

    Google Scholar 

  140. Shimada H, Sakakima H, Tsuchimochi K, Matsuda F, Komiya S, Goldring MB, Ijiri K. Senescence of chondrocytes in aging articular cartilage: GADD45β mediates p21 expression in association with C/EBPβ in senescence-accelerated mice. Pathol Res Pract. 2011;207:225–31.

    Google Scholar 

  141. Matsuzaki T, Alvarez-Garcia O, Mokuda S, Nagira K, Olmer M, Gamini R, Miyata K, Akasaki Y, Su AI, Asahara H, Lotz MK. FoxO transcription factors modulate autophagy and proteoglycan 4 in cartilage homeostasis and osteoarthritis. Sci Transl Med. 2018;10(428):pii eaan0746. doi 10. 1126/scitranslmed,aan0746.

    Google Scholar 

  142. Akasaki Y, Alvarez-Garcia O, Saito M, Caramés B, Iwamoto Y, Lotz MK. FoxO transcription factors support oxidative stress resistance in human chondrocytes. Arthritis Rheum. 2014;66(12):3349–58.

    Article  CAS  Google Scholar 

  143. Akasaki Y, Hasegawa A, Saito M, Asahara H, Iwamoto Y, Lotz MK, Dysregulated FOXO. Transcription factors in articular cartilage in aging and osteoarthritis. Osteoarthritis Cartilage. 2014;22:162–70.

    Article  CAS  PubMed  Google Scholar 

  144. Breu A, Sprinzing B, Merkl K, Bechmann V, Kujat R, Jenei-Lanzl Z, Prantl L, Angele P. Estrogen reduces cellular aging in human mesenchymal stem cells and chondrocytes. J Orthop Res. 2011;29:1563–71.

    Article  CAS  PubMed  Google Scholar 

  145. Yudoh K, Karasawa R. Statin prevents chondrocyte aging and degeneration of articular cartilage in osteoarthritis (OA). Aging (Albany NY). 2010;2:990–8.

    Article  CAS  Google Scholar 

  146. Henrotin Y, Deby-Dupont G, Deby C, Franchimont P, Emerit I. Active oxygen species, articular inflammation and cartilage damage. EXS. 1992;62:308–22.

    CAS  PubMed  Google Scholar 

  147. Schiller J, Fuchs B, Arnhold J, Arnold K. Contribution of reactive oxygen species to cartilage degradation in rheumatic diseases: molecular pathways, diagnosis and potential therapeutic strategies. Curr Med Chem. 2003;10:2123–45.

    Article  CAS  PubMed  Google Scholar 

  148. Henrotin YE, Bruckner P, Pujol JP. The role of reactive oxygen species in homeostasis and degradation of cartilage. Osteoarthritis Cartilage. 2003;11:747–55.

    Article  CAS  PubMed  Google Scholar 

  149. Tomiyama T, Fukuda K, Yamazaki K, Hashimoto K, Ueda H, Mori S, Hamanishi C. Cyclic compression loaded on cartilage explants enhances the production of reactive oxygen species. J Rheumatol. 2007;34:556–62.

    CAS  PubMed  Google Scholar 

  150. Anderson DD, Brown TD, Radin EL. The influence of basal cartilage calcification on dynamic juxtaarticular stress transmission. Clin Orthop Relat Res. 1993;(268):298–307.

    Google Scholar 

  151. Kelly PA, O’Connor JJ. Transmission of rapidly applied loads through articular cartilage. Part 1: uncracked cartilage. Proc Insts Mech Eng H. 1996;210:27–37.

    Article  CAS  Google Scholar 

  152. Kelly PA, O’Connor JJ. Transmission of rapidly applied loads through articular cartilage. Part 2: cracked cartilage. Proc Insts Mech Eng H. 1996;210:39–49.

    Article  CAS  Google Scholar 

  153. Nguyen Q, Murphy G, Hughes CE, Mort JS, Roughley PJ. Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Biochem J. 1993;295(Pt 2):595–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Roughley PJ, Nguyen Q, Mort JS, Hughes CE, Caterson B. Proteolytic degradation in human articular cartilage: its relationship to stromelysin. Agents Actions Suppl. 1993;39:149–59.

    CAS  PubMed  Google Scholar 

  155. Aquaron R. Alkaptonuria: a very rare metabolic disorder. Indian J Biochem Biophys. 2013;50:339–44.

    CAS  PubMed  Google Scholar 

  156. Grosicka A, Kucharz EJ. Alkaptonuria. Wiad Lek. 2009;62:197–203.

    PubMed  Google Scholar 

  157. Introne WJ, Gahl WA. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, LJH B, Bird TD, Fong CT, Mefford HC, RJH S, Stephens K, editors. Alkaptonuria. Seattle (WA): University of Washington, Seattle; 1993.

    Google Scholar 

  158. Pritzker K. Articular pathology of gout, calcium pyrophosphate dihydrate, and basic calcium phosphate crystal deposition arthropathies. In: Terkeltaub R, editor. Gout and other crystal arthropathies. Philadelphia: Elsevier, Saunders; 2012. p. 1–19.

    Google Scholar 

  159. Pritzker KP. Calcium pyrophosphate crystal arthropathy: a biomineralization disorder. Hum Pathol. 1986;17:543–5.

    Article  CAS  PubMed  Google Scholar 

  160. Ryan LM. Calcium pyrophosphate dihydrate crystal deposition and other crystal deposition diseases. Curr Opin Rheumatol. 1993;5:517–21.

    Article  CAS  PubMed  Google Scholar 

  161. Pritzker KP. Crystal deposition in joints: prevalence and relevance for arthritis. J Rheumatol. 2008;35:958–9.

    Article  PubMed  Google Scholar 

  162. Rosenthal AK, McCarty BA, Cheung HS, Ryan LM. A comparison of the effect of transforming growth factor beta 1 on pyrophosphate elaboration from various articular tissues. Arthritis Rheum. 1993;36:539–42.

    Article  CAS  PubMed  Google Scholar 

  163. Pritzker KPH, Luk SC. Apatite associated arthropathies: preliminary ultrastructural studies. Scan Electron Microsc. 1976;493–500.

    Google Scholar 

  164. Molloy ES, McCarthy GM. Hydroxyapatite deposition disease of the joint. Curr Rheumatol Rep. 2003;5:215–21.

    Article  PubMed  Google Scholar 

  165. Hogan DB, Pritzker KP. Synovial fluid analysis – another look at the mucin clot test. J Rheumatol. 1985;12:242–4.

    CAS  PubMed  Google Scholar 

  166. Shinozaki T, Xu Y, Cruz TF, Pritzker KPH. Calcium pyrophosphate dihydrate (CPPD) crystal dissolution by alkaline phosphatase: interaction of alkaline phosphatase on CPPD crystals. J Rheumatol. 1995;22:117–23.

    CAS  PubMed  Google Scholar 

  167. So PP, Tsui FW, Vieth R, Tupy JH, Pritzker KP. Inhibition of alkaline phosphatase by cysteine: implications for calcium pyrophosphate dihydrate crystal deposition disease. J Rheumatol. 2007;34:1313–22.

    CAS  PubMed  Google Scholar 

  168. Kannampuzha JV, Tupy JH, Pritzker KP. Mercaptopyruvate inhibits tissue-nonspecific alkaline phosphatase and calcium pyrophosphate dihydrate crystal dissolution. J Rheumatol. 2009;36:2758–65.

    Article  CAS  PubMed  Google Scholar 

  169. Myasoedova E, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. Is the incidence of rheumatoid arthritis rising? Results from Olmsted County, Minnesota, 1955–2007. Arthritis Rheum. 2010;62:1576–82.

    Article  PubMed  PubMed Central  Google Scholar 

  170. Conigliaro P, Chimenti MS, Triggianese P, Sunzini F, Novelli L, Perricone C, Perricone R. Autoantibodies in inflammatory arthritis. Autoimmun Rev. 2016;15:673–83.

    Article  CAS  PubMed  Google Scholar 

  171. Harris ED Jr. Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med. 1990;322:1277–89.

    Article  PubMed  Google Scholar 

  172. Zhou RP, Dai BB, Xie YY, Wu XS, Wang ZS, Li Y, Wang ZQ, Zu SQ, Ge JF, Chen FH. Interleukin-1β and tumor necrosis factor-α augment acidosis-induced rat articular chondrocyte apoptosis via nuclear factor-kappaB-dependent upregulation of ASIC1a channel. Biochim Biophys Acta. 2018;1864(1):162–77.

    Article  CAS  Google Scholar 

  173. Abramson SB, Amin A. Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage. Rheumatology (Oxford). 2002;41(9):972–80.

    Article  CAS  Google Scholar 

  174. Malemud CJ. Matrix metalloproteinases and synovial joint pathology. Prog Mol Biol Transl Sci. 2017;148:305–25.

    Article  PubMed  Google Scholar 

  175. Caglič D, Repnik U, Jedeszko C, Kosec G, Miniejew C, Kindermann M, Vasiljeva O, Turk V, Wendt KU, Sloane BF, Goldring MB, Turk B. The proinflammatory cytokines interleukin-1α and tumor necrosis factor α promote the expression and secretion of proteolytically active cathepsin S from human chondrocytes. Biol Chem. 2013;394(2):307–16.

    Article  PubMed  CAS  Google Scholar 

  176. Hollander AP, Atkinst RM, Eastwoodt DM, et al. Human cartilage is degraded by rheumatoid arthritis synovial fluid but not by recombinant cytokines in vitro. Clin Exp Immunol. 1991;83:52–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Ostrowska M, Maśliński W, Prochorec-Sobieszek M, Nieciecki M, Sudoł-Szopińska I. Cartilage and bone damage in rheumatoid arthritis. Reumatologia. 2018;56(2):111–20.

    Article  PubMed  PubMed Central  Google Scholar 

  178. Sudoł-Szopińska I, Kontny E, Zaniewicz-Kaniewska K, et al. Role of inflammatory factors and adipose tissue in pathogenesis of rheumatoid arthritis and osteoarthritis. Part I: Rheumatoid adipose tissue. J Ultrason. 2013;13:192–201.

    Article  PubMed  PubMed Central  Google Scholar 

  179. Sudoł-Szopińska I, Kontny E, Maśliński W, et al. The pathogenesis of rheumatoid arthritis in radiological studies. Part I: formation of inflammatory infiltrates within the synovial membrane. J Ultrason. 2012;12:202–13.

    Article  PubMed  PubMed Central  Google Scholar 

  180. Kontny E, Plebanczyk M, Lisowska B, Olszewska M, Maldyk P, Maslinski W. Comparison of rheumatoid articular adipose and synovial tissue reactivity to proinflammatory stimuli: contribution to adipocytokine network. Ann Rheum Dis. 2012;71(2):262–7.

    Article  CAS  PubMed  Google Scholar 

  181. Pritzker KHP. Pathology of osteoarthritis. In: Brandt KD, Doherty M, Lohmander LS, Edition 2nd, editors. Osteoarthritis. Oxford: Oxford University Press; 2003. p. 49–58.

    Google Scholar 

  182. Buckwalter JA, Mankin HJ. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect. 1998;47:487–504.

    CAS  PubMed  Google Scholar 

  183. Buckwalter JA, Mankin HJ, Grodzinsky AJ. Articular cartilage and osteoarthritis. Instr Course Lect. 2005;54:465–80.

    PubMed  Google Scholar 

  184. Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, Heyse SP, Hirsch R, Hochberg MC, Hunder GG, Liang MH, Pillemer SR, Steen VD, Wolfe F. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998;41:778–99.

    Article  CAS  PubMed  Google Scholar 

  185. Jeon OH, David N, Campisi J, Elisseeff JH. Senescent cells and osteoarthritis: a painful connection. J Clin Invest. 2018;128(4):1229–37.

    Article  PubMed  PubMed Central  Google Scholar 

  186. Bierma-Zeinstra SM, van Middelkoop M. Osteoarthritis: in search of phenotypes. Nat Rev Rheumatol. 2017;13:705–6.

    Google Scholar 

  187. Deveza LA, Melo L, Yamato TP, Mills K, Ravi V, Hunter DJ. Knee osteoarthritis phenotypes and their relevance for outcomes: a systematic review. Osteoarthritis Cartilage. 2017;25(12):1926–41.

    Google Scholar 

  188. Budd E, Nalesso G, Mobasheri A. Extracellular genomic biomarkers of osteoarthritis. Expert Rev Mol Diagn. 2018:18(1):55–74.

    Google Scholar 

  189. Nuki G. Osteoarthritis: a problem of joint failure. Z Rheumatol. 1999;58(3):142–7.

    Google Scholar 

  190. Varady NH, Grodzinsky AJ. Osteoarthritis year in review 2015: mechanics. Osteoarthritis Cartilage. 2016;24:27–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Christensen R, Henriksen M, Leeds AR, Gudbergsen H, Christensen P, Sorensen TJ, Bartels EM, Riecke BF, Aaboe J, Frederiksen R, Boesen M, Lohmander LS, Astrup A, Bliddal H. Effect of weight maintenance on symptoms of knee osteoarthritis in obese patients: a twelve-month randomized controlled trial. Arthritis Care Res. 2015;67:640–50.

    Article  Google Scholar 

  192. Lee R, Kean WF. Obesity and knee osteoarthritis. Inflammopharmacology. 2012;20:53–8.

    Article  PubMed  Google Scholar 

  193. Jiménez G, Cobo-Molinos J, Antich C, López-Ruiz E. Osteoarthritis: Trauma vs Disease. Adv Exp Med Biol. 2018;1059:63–83.

    Article  PubMed  CAS  Google Scholar 

  194. Andriacchi TP, Favre J. The nature of in vivo mechanical signals that influence cartilage health and progression to knee osteoarthritis. Curr Rheumatol Rep. 2014;16:463.

    Article  PubMed  Google Scholar 

  195. Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, Salter D, van den Berg WB. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage. 2006;14:13–29.

    Article  CAS  PubMed  Google Scholar 

  196. Setton LA, Mow VC, Muller FJ, Pita JC, Howell DS. Altered structure-function relationships for articular cartilage in human osteoarthritis and an experimental canine model. Agents Actions Suppl. 1993;39:27–48.

    Article  CAS  PubMed  Google Scholar 

  197. Lohmander LS, Felson DT. Defining the role of molecular markers to monitor disease, intervention, and cartilage breakdown in osteoarthritis. J Rheumatol. 1997;24:782–5.

    CAS  PubMed  Google Scholar 

  198. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986;29:1039–49.

    Article  CAS  PubMed  Google Scholar 

  199. Oegema TR Jr, Carpenter RJ, Hofmeister F, Thompson RC Jr. The interaction of the zone of calcified cartilage and subchondral bone in osteoarthritis. Microsc Res Tech. 1997;37:324–32.

    Article  PubMed  Google Scholar 

  200. Vinatier C, Domínguez E, Guicheux J, Caramés B. Role of the inflammation-autophagy-senescence integrative network in osteoarthritis. Front Physiol. 2018;9:706.

    Google Scholar 

  201. Dieppe PA. Recommended methodology for assessing the progression of osteoarthritis of the hip and knee joints. Osteoarthritis Cartilage. 1995;3:73–7.

    Article  CAS  PubMed  Google Scholar 

  202. Mankin HJ, Thrasher AZ. Water content and binding in normal and osteoarthritic human cartilage. J Bone Joint Surg Am. 1975;57:76–80.

    Article  CAS  PubMed  Google Scholar 

  203. Venn M, Maroudas A. Chemical composition and swelling of normal and osteoarthrotic femoral head cartilage. I. Chemical composition. Ann Rheum Dis. 1977;36:121–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Maroudas A, Ziv I, Weisman N, Venn M. Studies of hydration and swelling pressure in normal and osteoarthritic cartilage. Biorheology. 1985;22:159–69.

    Article  CAS  PubMed  Google Scholar 

  205. Lothe K, Spycher MA, Ruttner JR. Focal lacunar resorption in the articular cartilage of femoral heads. J Bone Joint Surg. 1985;67:543–7.

    Article  CAS  Google Scholar 

  206. Hashimoto S, Ochs RL, Komiya S, Lotz M. Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis. Arthritis Rheum. 1998;41:1632–8.

    Article  CAS  PubMed  Google Scholar 

  207. Mankin HJ, Dorfman H, Lippiello L, Zarins A. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am. 1971;53:523–37.

    Article  CAS  PubMed  Google Scholar 

  208. Mankin HJ, Lippiello L. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. J Bone Joint Surg Am. 1970;52:424–34.

    Article  CAS  PubMed  Google Scholar 

  209. Lee GM, Paul TA, Slabaugh M, Kelley SS. The incidence of enlarged chondrons in normal and osteoarthritic human cartilage and their relative matrix density. Osteoarthritis Cartilage. 2000;8:44–52.

    Article  CAS  PubMed  Google Scholar 

  210. Lotz MK, Otsuki S, Grogan SP, Sah R, Terkeltaub R, D’Lima D. Cartilage cell clusters. Arthritis Rheum. 2010;62:2206–18.

    Article  PubMed  PubMed Central  Google Scholar 

  211. Tetlow LC, Adlam DJ, Woolley DE. Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: associations with degenerative changes. Arthritis Rheum. 2001;44:585–94.

    Article  CAS  PubMed  Google Scholar 

  212. Sanchez C, Lambert C, Dubuc JE, Bertrand J, Pap T, et al. Syndecan-4 is increased in osteoarthritic knee, but not hip or shoulder, articular hypertrophic chondrocytes. Cartilage. 2019:1947603519870855. doi: 10.1177/1947603519870855. [Epub ahead of print]

    Google Scholar 

  213. Singh P, Marcu KB, Goldring MB, Otero M. Phenotypic instability of chondrocytes in osteoarthritis: on a path to hypertrophy. Ann N Y Acad Sci. 2019;1442(1):17–34.

    Google Scholar 

  214. Gratal P, Mediero A, Sánchez-Pernaute O, Prieto-Potin I, Lamuedra A, et al. Chondrocyte enlargement is a marker of osteoarthritis severity. Osteoarthritis Cartilage. 2019;27(8):1229–34.

    Google Scholar 

  215. Setton LA, Elliott DM, Mow VC. Altered mechanics of cartilage with osteoarthritis: human osteoarthritis and an experimental model of joint degeneration. Osteoarthritis Cartilage. 1999;7:2–14.

    Article  CAS  PubMed  Google Scholar 

  216. Maroudas A, Evans H, Almeida L. Cartilage of the hip joint. Topographical variation of glycosaminoglycan content in normal and fibrillated tissue. Ann Rheum Dis. 1973;32:1–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Cs-Szabo G, Melching LI, Roughley PJ, Glant TT. Changes in messenger RNA and protein levels of proteoglycans and link protein in human osteoarthritic cartilage samples. Arthritis Rheum. 1997;40:1037–45.

    Article  CAS  PubMed  Google Scholar 

  218. Barreto G, Soininen A, Ylinen P, Sandelin J, Konttinen YT, Nordstrom DC, Eklund KK. Soluble biglycan: a potential mediator of cartilage degradation in osteoarthritis. Arthritis Res Ther. 2015;17:379.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  219. Mort JS, Geng Y, Fisher WD, Roughley PJ. Aggrecan heterogeneity in articular cartilage from patients with osteoarthritis. BMC Musculoskelet Disord. 2016;17:89.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  220. Mollenhauer J, Mok MT, King KB, Gupta M, Chubinskaya S, Koepp H, Cole AA. Expression of anchorin CII (cartilage annexin V) in human young, normal adult, and osteoarthritic cartilage. J Histochem Cytochem. 1999;47:209–20.

    Article  CAS  PubMed  Google Scholar 

  221. Chevalier X, Groult N, Larget-Piet B, Zardi L, Hornebeck W. Tenascin distribution in articular cartilage from normal subjects and from patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum. 1994;37:1013–22.

    Article  CAS  PubMed  Google Scholar 

  222. Salter DM. Tenascin is increased in cartilage and synovium from arthritic knees. Br J Rheumatol. 1993;32:780–6.

    Article  CAS  PubMed  Google Scholar 

  223. Chen JR, Takahashi M, Suzuki M, Kushida K, Miyamoto S, Inoue T. Pentosidine in synovial fluid in osteoarthritis and rheumatoid arthritis: relationship with disease activity in rheumatoid arthritis. J Rheumatol. 1998;25:2440–4.

    CAS  PubMed  Google Scholar 

  224. Senolt L, Braun M, Olejarova M, Forejtova S, Gatterova J, Pavelka K. Increased pentosidine, an advanced glycation end product, in serum and synovial fluid from patients with knee osteoarthritis and its relation with cartilage oligomeric matrix protein. Ann Rheum Dis. 2005;64:886–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Willett TL, Kandel R, De Croos JN, Avery NC, Grynpas MD. Enhanced levels of non-enzymatic glycation and pentosidine crosslinking in spontaneous osteoarthritis progression. Osteoarthritis Cartilage. 2012;20:736–44.

    Article  CAS  PubMed  Google Scholar 

  226. Lane JM, Weiss C. Review of articular cartilage collagen research. Arthritis Rheum. 1975;18:553–62.

    Article  CAS  PubMed  Google Scholar 

  227. Pullig O, Weseloh G, Swoboda B. Expression of type VI collagen in normal and osteoarthritic human cartilage. Osteoarthritis Cartilage. 1999;7:191–202.

    Article  CAS  PubMed  Google Scholar 

  228. Girkontaite I, Frischholz S, Lammi P, Wagner K, Swoboda B, Aigner T. Von der Mark K. Immunolocalization of type X collagen in normal fetal and adult osteoarthritic cartilage with monoclonal antibodies. Matrix Biol. 1996;15:231–8.

    Article  CAS  PubMed  Google Scholar 

  229. Aigner T, Bertling W, Stoss H, Weseloh G, von der Mark K. Independent expression of fibril-forming collagens I, II, and III in chondrocytes of human osteoarthritic cartilage. J Clin Invest. 1993;91:829–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. Aigner T, Reichenberger E, Bertling W, Kirsch T, Stoss H, von der Mark K. Type X collagen expression in osteoarthritic and rheumatoid articular cartilage. Virchows Arch B Cell Pathol Incl Mol Pathol. 1993;63(4):205–11.

    Google Scholar 

  231. Weiss C. Ultrastructural characteristics of osteoarthritis. Fed Proc. 1973;32(4):1459–66.

    Google Scholar 

  232. Studer D, Chiquet M, Hunziker EB. Evidence for a distinct water-rich layer surrounding collagen fibrils in articular cartilage extracellular matrix. J Struct Biol. 1996;117:81–5.

    Article  CAS  PubMed  Google Scholar 

  233. Homandberg GA, Wen C, Hui F. Cartilage damaging activities of fibronectin fragments derived from cartilage and synovial fluid. Osteoarthritis Cartilage. 1998;6:231–44.

    Article  CAS  PubMed  Google Scholar 

  234. Jones KL, Brown M, Ali SY, Brown RA. An immunohistochemical study of fibronectin in human osteoarthritic and disease free articular cartilage. Ann Rheum Dis. 1987;46:809–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Chevalier X. Fibronectin, cartilage, and osteoarthritis. Semin Arthritis Rheum. 1993;22:307–18.

    Article  CAS  PubMed  Google Scholar 

  236. Swoboda B, Pullig O, Kladny B, Pfander D, Weseloh G. Collagen type VI content in healthy and arthritis knee joint cartilage. Zeitschrift fur Orthopadie und ihre Grenzgeb. 1999;137:540–4.

    Article  CAS  Google Scholar 

  237. von der Mark K, Frischholz S, Aigner T, Beier F, Belke J, Erdmann S, Burkhardt H. Upregulation of type X collagen expression in osteoarthritic cartilage. Acta Orthop Scand Suppl. 1995;266:125–9.

    Article  PubMed  Google Scholar 

  238. Khoshgoftar M, Torzilli PA, Maher SA. Influence of the pericellular and extracellular matrix structural properties on chondrocyte mechanics. J Orthop Res. 2018;36(2):721–29.

    Google Scholar 

  239. Henao-Murillo L, Ito K, van Donkelaar CC. Collagen damage location in articular cartilage differs if damage is caused by excessive loading magnitude or rate. Ann Biomed Eng. 2018;46(4):605–15.

    Article  PubMed  PubMed Central  Google Scholar 

  240. Imhof H, Breitenseher M, Kainberger F, Trattnig S. Degenerative joint disease: cartilage or vascular disease? Skelet Radiol. 1997;26:398–403.

    Article  CAS  Google Scholar 

  241. Trickey WR, Lee GM, Guilak F. Viscoelastic properties of chondrocytes from normal and osteoarthritic human cartilage. J Orthop Res. 2000;18:891–8.

    Article  CAS  PubMed  Google Scholar 

  242. Trickey WR, Vail TP, Guilak F. The role of the cytoskeleton in the viscoelastic properties of human articular chondrocytes. J Orthop Res. 2004;22:131–9.

    Article  PubMed  Google Scholar 

  243. Lai Y, Yu XP, Zhang Y, Tian Q, Song H, Mucignat MT, Perris R, Samuels J, Krasnokutsky S, Attur M, Greenberg JD, Abramson SB, Di Cesare PE, Liu CJ. Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA. Osteoarthritis Cartilage. 2012;20:854–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  244. Verma P, Dalal K. Serum cartilage oligomeric matrix protein (COMP) in knee osteoarthritis: a novel diagnostic and prognostic biomarker. J Orthop Res. 2013;31:999–1006.

    Article  CAS  PubMed  Google Scholar 

  245. Song SY, Han YD, Hong SY, Kim K, Yang SS, Min BH, Yoon HC. Chip-based cartilage oligomeric matrix protein detection in serum and synovial fluid for osteoarthritis diagnosis. Anal Biochem. 2012;420:139–46.

    Article  CAS  PubMed  Google Scholar 

  246. El-Arman MM, El-Fayoumi G, El-Shal E, El-Boghdady I, El-Ghaweet A. Aggrecan and cartilage oligomeric matrix protein in serum and synovial fluid of patients with knee osteoarthritis. HSS J. 2010;6(2):171–6.

    Google Scholar 

  247. Clark AG, Jordan JM, Vilim V, Renner JB, Dragomir AD, Luta G, Kraus VB. Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: the Johnston County Osteoarthritis Project. Arthritis Rheum. 1999;42:2356–64.

    Article  CAS  PubMed  Google Scholar 

  248. Hosnijeh FS, Runhaar J, van Meurs JB, Bierma-Zeinstra SM. Biomarkers for osteoarthritis: can they be used for risk assessment? A systematic review. Maturitas. 2015;82:36–49.

    Article  PubMed  CAS  Google Scholar 

  249. Neidhart M, Hauser N, Paulsson M, DiCesare PE, Michel BA, Hauselmann HJ. Small fragments of cartilage oligomeric matrix protein in synovial fluid and serum as markers for cartilage degradation. Br J Rheumatol. 1997;36:1151–60.

    Article  CAS  PubMed  Google Scholar 

  250. Chateauvert JMD, Grynpas MD, Kessler MJ, Pritzker KPH. Spontaneous osteoarthritis in rhesus macaques. II. Characterization of disease and morphometric studies. J Rheumatol. 1990;17:73–83.

    CAS  PubMed  Google Scholar 

  251. Felson DT, Zhang Y, Hannan MT, Naimark A, Weissman BN, Aliabadi P, Levy D. The incidence and natural history of knee osteoarthritis in the elderly. Arthritis Rheum. 1995;38:1500–5.

    Article  CAS  PubMed  Google Scholar 

  252. Veronese N, Maggi S, Trevisan C, Noale M, De Rui M, Bolzetta F, Zambon S, Musacchio E, Sartori L, Perissinotto E, Stubbs B, Crepaldi G, Manzato E, Sergi G. Pain increases the risk of developing frailty in older adults with osteoarthritis. Pain Med. 2017;18:414–27.

    PubMed  Google Scholar 

  253. Loeser RF. The effects of aging on the development of osteoarthritis. HSS J. 2012;8:18–9.

    Google Scholar 

  254. Varela-Eirin M, Loureiro J, Fonseca E, Corrochano S, Caeiro JR, et al. Cartilage regeneration and ageing: targeting cellular plasticity in osteoarthritis. Ageing Res Rev. 2018;42:56–71.

    Google Scholar 

  255. Sokoloff L. Osteoarthritis and aging. In: Sokoloff L, editor. Biology of degenerative joint disease. Chicago: University of Chicago Press, Chicago; 1969. p. 24–7.

    Google Scholar 

  256. Mitrovic D, Quintero M, Stankovic A, Ryckewaert A. Cell density of adult human femoral condylar articular cartilage. Joints with normal and fibrillated surfaces. Lab Investig. 1983;49:309–16.

    CAS  PubMed  Google Scholar 

  257. Lane LB, Villacin A, Bullough PG. The vascularity and remodelling of subchondrial bone and calcified cartilage in adult human femoral and humeral heads. An age- and stress-related phenomenon. J Bone Joint Surg Br. 1977;59:272–8.

    Article  CAS  PubMed  Google Scholar 

  258. Venn MF. Variation of chemical composition with age in human femoral head cartilage. Ann Rheum Dis. 1978;37:168–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kenneth P. H. Pritzker MD, FRCPC .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Science+Business Media, LLC, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Pritzker, K.P.H., Gahunia, H.K. (2020). Articular Cartilage: Homeostasis, Aging and Degeneration. In: Gahunia, H., Gross, A., Pritzker, K., Babyn, P., Murnaghan, L. (eds) Articular Cartilage of the Knee. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7587-7_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7587-7_3

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-7585-3

  • Online ISBN: 978-1-4939-7587-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics