Skip to main content
SpringerLink
Log in

Pathogenesis of Osteoarthritis

  • Chapter
Osteoarthritis

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
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. Zhang Y, Jordan JM. Epidemiology of osteoarthritis. Clin Geriatr Med. 2010;26(3):355–69.

    PubMed Central  PubMed  Google Scholar 

  2. Loeser RF. Age-related changes in the musculoskeletal system and the development of osteoarthritis. Clin Geriatr Med. 2010;26(3):371–86.

    PubMed Central  PubMed  Google Scholar 

  3. Lawrence RC, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008;58(1):26–35.

    PubMed Central  PubMed  Google Scholar 

  4. Anderson JJ, Felson DT. Factors associated with osteoarthritis of the knee in the first national Health and Nutrition Examination Survey (HANES I). Evidence for an association with overweight, race, and physical demands of work. Am J Epidemiol. 1988;128(1):179–89.

    CAS  PubMed  Google Scholar 

  5. Felson DT, et al. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med. 2000;133(8):635–46.

    CAS  PubMed  Google Scholar 

  6. Srikanth VK, et al. A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis. Osteoarthritis Cartilage. 2005;13(9):769–81.

    PubMed  Google Scholar 

  7. Spector TD, et al. Genetic influences on osteoarthritis in women: a twin study. BMJ. 1996;312(7036):940–3.

    PubMed Central  CAS  PubMed  Google Scholar 

  8. Palotie A, et al. Predisposition to familial osteoarthrosis linked to type II collagen gene. Lancet. 1989;1(8644):924–7.

    CAS  PubMed  Google Scholar 

  9. Kerkhof HJ, et al. A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22. Arthritis Rheum. 2010;62(2):499–510.

    PubMed Central  CAS  PubMed  Google Scholar 

  10. Felson DT, et al. Weight loss reduces the risk for symptomatic knee osteoarthritis in women. The Framingham study. Ann Intern Med. 1992;116(7):535–9.

    CAS  PubMed  Google Scholar 

  11. Christensen R, et al. Effect of weight reduction in obese patients diagnosed with knee osteoarthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2007;66(4):433–9.

    PubMed Central  PubMed  Google Scholar 

  12. van Saase JL, et al. Osteoarthritis and obesity in the general population. A relationship calling for an explanation. J Rheumatol. 1988;15(7):1152–8.

    PubMed  Google Scholar 

  13. Loughlin J, et al. Association of the interleukin-1 gene cluster on chromosome 2q13 with knee osteoarthritis. Arthritis Rheum. 2002;46(6):1519–27.

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  15. Brandt KD, et al. Yet more evidence that osteoarthritis is not a cartilage disease. Ann Rheum Dis. 2006;65(10):1261–4.

    PubMed Central  CAS  PubMed  Google Scholar 

  16. Buckwalter JA, Mankin HJ. Articular cartilage: tissue design and chondrocyte-matrix interactions. Instr Course Lect. 1998;47:477–86.

    CAS  PubMed  Google Scholar 

  17. Poole AR, et al. Composition and structure of articular cartilage: a template for tissue repair. Clin Orthop Relat Res. 2001;391:S26–33.

    PubMed  Google Scholar 

  18. Eyre D. Collagen of articular cartilage. Arthritis Res. 2002;4(1):30–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  19. Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage: structure, composition, and function. Sports Health Multidiscip Approach. 2009;1(6):461–8.

    Google Scholar 

  20. Roughley PJ, Lee ER. Cartilage proteoglycans: structure and potential functions. Microsc Res Tech. 1994;28(5):385–97.

    CAS  PubMed  Google Scholar 

  21. Watanabe H, Yamada Y, Kimata K. Roles of aggrecan, a large chondroitin sulfate proteoglycan, in cartilage structure and function. J Biochem. 1998;124(4):687–93.

    CAS  PubMed  Google Scholar 

  22. Hardingham TE, Fosang AJ, Dudhia J. The structure, function and turnover of aggrecan, the large aggregating proteoglycan from cartilage. Eur J Clin Chem Clin Biochem J Forum Eur Clin Chem Soc. 1994;32(4):249–57.

    CAS  Google Scholar 

  23. Knudson CB, Knudson W. Cartilage proteoglycans. Semin Cell Dev Biol. 2001;12(2):69–78.

    CAS  PubMed  Google Scholar 

  24. Poole AR, et al. Contents and distributions of the proteoglycans decorin and biglycan in normal and osteoarthritic human articular cartilage. J Orthop Res. 1996;14(5):681–9.

    CAS  PubMed  Google Scholar 

  25. Hedlund H, et al. Fibromodulin distribution and association with collagen. Matrix Biol. 1994;14(3):227–32.

    CAS  PubMed  Google Scholar 

  26. Clark JM. The organisation of collagen fibrils in the superficial zones of articular cartilage. J Anat. 1990;171:117–30.

    PubMed Central  CAS  PubMed  Google Scholar 

  27. REDLER I, et al. The ultrastructure and biomechanical significance of the tidemark of articular cartilage. Clin Orthop Relat Res. 1975;112:357–62.

    PubMed  Google Scholar 

  28. Arkill KP, Winlove CP. Solute transport in the deep and calcified zones of articular cartilage. Osteoarthritis Cartilage. 2008;16(6):708–14.

    CAS  PubMed  Google Scholar 

  29. Green Jr WT, et al. Microradiographic study of the calcified layer of articular cartilage. Arch Pathol. 1970;90(2):151–8.

    CAS  PubMed  Google Scholar 

  30. Samuels J, Krasnokutsky S, Abramson SB. Osteoarthritis: a tale of three tissues. Bull NYU Hosp Jt Dis. 2008;66(3):244–50.

    PubMed  Google Scholar 

  31. Hui AY, et al. A systems biology approach to synovial joint lubrication in health, injury, and disease. Wiley Interdiscip Rev Syst Biol Med. 2012;4(1):15–37.

    PubMed Central  CAS  PubMed  Google Scholar 

  32. Ateshian G, Mow V, Huiskes R. Friction, lubrication, and wear of articular cartilage and diarthrodial joints. Basic Orthop Biomech Mechanobiol. 2005;3:447–94.

    Google Scholar 

  33. Blewis M, et al. A model of synovial fluid lubricant composition in normal and injured joints. European Cells and Materials. 2007;13:26-39.

    Google Scholar 

  34. Jay GD, et al. The role of lubricin in the mechanical behavior of synovial fluid. Proc Natl Acad Sci U S A. 2007;104(15):6194–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  35. Ogston A, Stanier J. The physiological function of hyaluronic acid in synovial fluid; viscous, elastic and lubricant properties. J Physiol. 1953;119(2–3):244–52.

    PubMed Central  CAS  PubMed  Google Scholar 

  36. Hascall VC, Kuettner KE (eds.). Publisher: Birkhäuser Basel. Schmid TM, et al. Superficial zone protein (SZP) is an abundant glycoprotein in human synovial fluid with lubricating properties. In: The many faces of osteoarthritis. 2002. p. 159–61.

    Google Scholar 

  37. Kapoor M, et al. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7(1):33–42.

    CAS  PubMed  Google Scholar 

  38. Goldring MB. Osteoarthritis and cartilage: the role of cytokines. Curr Rheumatol Rep. 2000;2(6):459–65.

    CAS  PubMed  Google Scholar 

  39. Blewis ME, et al. Interactive cytokine regulation of synoviocyte lubricant secretion. Tissue Eng Part A. 2010;16(4):1329–37.

    PubMed Central  CAS  PubMed  Google Scholar 

  40. Futani H, et al. Relation between interleukin-18 and PGE2 in synovial fluid of osteoarthritis: a potential therapeutic target of cartilage degradation. J Immunother. 2002;25 Suppl 1:S61–4.

    CAS  PubMed  Google Scholar 

  41. Denko CW, Boja B, Moskowitz RW. Growth factors, insulin-like growth factor-1 and growth hormone, in synovial fluid and serum of patients with rheumatic disorders. Osteoarthritis Cartilage. 1996;4(4):245–9.

    CAS  PubMed  Google Scholar 

  42. Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol. 2011;23(5):471–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  43. Poole AR. Cartilage in health and disease. In: Koopman W, editor. Arthritis and allied conditions. A textbook of rheumatology. Philadelphia: Lippincott Williams and Wilkins; 2001.

    Google Scholar 

  44. Nagase H, Woessner Jr JF. Matrix metalloproteinases. J Biol Chem. 1999;274(31):21491–4.

    CAS  PubMed  Google Scholar 

  45. Konttinen YT, et al. Analysis of 16 different matrix metalloproteinases (MMP-1 to MMP-20) in the synovial membrane: different profiles in trauma and rheumatoid arthritis. Ann Rheum Dis. 1999;58(11):691–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  46. Tchetverikov I, et al. MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis. Ann Rheum Dis. 2005;64(5):694–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Ishiguro N, et al. Relationship of matrix metalloproteinases and their inhibitors to cartilage proteoglycan and collagen turnover: analyses of synovial fluid from patients with osteoarthritis. Arthritis Rheum. 1999;42(1):129–36.

    CAS  PubMed  Google Scholar 

  48. Roos H, et al. Markers of cartilage matrix metabolism in human joint fluid and serum: the effect of exercise. Osteoarthritis Cartilage. 1995;3(1):7–14.

    CAS  PubMed  Google Scholar 

  49. Knauper V, et al. Cellular activation of proMMP-13 by MT1-MMP depends on the C-terminal domain of MMP-13. FEBS Lett. 2002;532(1–2):127–30.

    CAS  PubMed  Google Scholar 

  50. Zhang E, et al. Aggrecanases in the human synovial fluid at different stages of osteoarthritis. Clin Rheumatol. 2013;32(6):797–803.

    PubMed  Google Scholar 

  51. Porter S, et al. The ADAMTS metalloproteinases. Biochem J. 2005;386(Pt 1):15–27.

    PubMed Central  CAS  PubMed  Google Scholar 

  52. Caterson B, et al. Mechanisms involved in cartilage proteoglycan catabolism. Matrix Biol. 2000;19(4):333–44.

    CAS  PubMed  Google Scholar 

  53. Stanton H, et al. ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature. 2005;434(7033):648–52.

    CAS  PubMed  Google Scholar 

  54. Jones GC, Riley GP. ADAMTS proteinases: a multi-domain, multi-functional family with roles in extracellular matrix turnover and arthritis. Arthritis Res Ther. 2005;7(4):160–9.

    PubMed Central  PubMed  Google Scholar 

  55. Yoshihara Y, et al. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis. 2000;59(6):455–61.

    PubMed Central  CAS  PubMed  Google Scholar 

  56. Martel-Pelletier J, et al. Excess of metalloproteases over tissue inhibitor of metalloprotease may contribute to cartilage degradation in osteoarthritis and rheumatoid arthritis. Lab Invest. 1994;70(6):807–15.

    CAS  PubMed  Google Scholar 

  57. Yehia SR, Duncan H. Synovial fluid analysis. Clin Orthop Relat Res. 1975;107:11–24.

    PubMed  Google Scholar 

  58. Kratz A, et al. Appendix: laboratory values of clinical importance. In: Longo DL et al., editors. Harrison’s principles of internal medicine. 18th ed. New York: The McGraw-Hill Companies; 2012.

    Google Scholar 

  59. Castor CW. The microscopic structure of normal human synovial tissue. Arthritis Rheum. 1960;3(2):140–51.

    CAS  PubMed  Google Scholar 

  60. Barland P, Novikoff AB, Hamerman D. Electron microscopy of the human synovial membrane. J Cell Biol. 1962;14(2):207–20.

    PubMed Central  CAS  PubMed  Google Scholar 

  61. Ropes MW, Rossmeisl EC, Bauer W. The origin and nature of normal human synovial fluid. J Clin Invest. 1940;19(6):795.

    PubMed Central  CAS  PubMed  Google Scholar 

  62. Sabaratnam S, et al. Size selectivity of hyaluronan molecular sieving by extracellular matrix in rabbit synovial joints. J Physiol. 2005;567(Pt 2):569–81.

    PubMed Central  CAS  PubMed  Google Scholar 

  63. Kushner I, Somerville JA. Permeability of human synovial membrane to plasma proteins. Relationship to molecular size and inflammation. Arthritis Rheum. 1971;14(5):560–70.

    CAS  PubMed  Google Scholar 

  64. Pejovic M, Stankovic A, Mitrovic DR. Determination of the apparent synovial permeability in the knee joint of patients suffering from osteoarthritis and rheumatoid arthritis. Br J Rheumatol. 1995;34(6):520–4.

    CAS  PubMed  Google Scholar 

  65. Burr DB, Gallant MA. Bone remodelling in osteoarthritis. Nat Rev Rheumatol. 2012;8(11):665–73.

    CAS  PubMed  Google Scholar 

  66. Henrotin Y, Pesesse L, Sanchez C. Subchondral bone and osteoarthritis: biological and cellular aspects. Osteoporos Int. 2012;23 Suppl 8:S847–51.

    PubMed  Google Scholar 

  67. Madry H, van Dijk CN, Mueller-Gerbl M. The basic science of the subchondral bone. Knee Surg Sports Traumatol Arthrosc. 2010;18(4):419–33.

    PubMed  Google Scholar 

  68. Li G, et al. Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes. Arthritis Res Ther. 2013;15(6):223.

    PubMed Central  CAS  PubMed  Google Scholar 

  69. Goldring MB, Goldring SR. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci. 2010;1192:230–7.

    CAS  PubMed  Google Scholar 

  70. Clark J, Huber J. The structure of the human subchondral plate. J Bone Joint Surg,Br. 1990;72-B(5):866–73.

    Google Scholar 

  71. Holmdahl DE, Ingelmark BE. The contact between the articular cartilage and the medullary cavities of the bone. Acta Orthop Scand. 1950;20(2):156–65.

    CAS  PubMed  Google Scholar 

  72. Inoue H. Alterations in the collagen framework of osteoarthritic cartilage and subchondral bone. Int Orthop. 1981;5(1):47–52.

    CAS  PubMed  Google Scholar 

  73. Goldring SR. Alterations in periarticular bone and cross talk between subchondral bone and articular cartilage in osteoarthritis. Ther Adv Musculoskelet Dis. 2012;4(4):249–58.

    PubMed Central  PubMed  Google Scholar 

  74. Lanyon LE. Osteocytes, strain detection, bone modeling and remodeling. Calcif Tissue Int. 1993;53 Suppl 1:S102–6; discussion S106–7.

    CAS  PubMed  Google Scholar 

  75. Martin RB. Targeted bone remodeling involves BMU steering as well as activation. Bone. 2007;40(6):1574–80.

    CAS  PubMed  Google Scholar 

  76. Imhof H, et al. Importance of subchondral bone to articular cartilage in health and disease. Top Magn Reson Imaging. 1999;10(3):180–92.

    CAS  PubMed  Google Scholar 

  77. Suri S, Walsh DA. Osteochondral alterations in osteoarthritis. Bone. 2012;51(2):204–11.

    PubMed  Google Scholar 

  78. Issa S, Sharma L. Epidemiology of osteoarthritis: an update. Curr Rheumatol Rep. 2006;8(1):7–15.

    PubMed  Google Scholar 

  79. Felson DT, et al. The incidence and natural history of knee osteoarthritis in the elderly. The Framingham Osteoarthritis study. Arthritis Rheum. 1995;38(10):1500–5.

    CAS  PubMed  Google Scholar 

  80. Saddik D, McNally EG, Richardson M. MRI of Hoffa’s fat pad. Skeletal Radiol. 2004;33(8):433–44.

    CAS  PubMed  Google Scholar 

  81. Jacobson JA, et al. MR imaging of the infrapatellar fat pad of Hoffa. Radiographics. 1997;17(3):675–91.

    CAS  PubMed  Google Scholar 

  82. Gallagher J, et al. The infrapatellar fat pad: anatomy and clinical correlations. Knee Surg Sports Traumatol Arthrosc. 2005;13(4):268–72.

    CAS  PubMed  Google Scholar 

  83. Vahlensieck M, et al. Hoffa’s recess: incidence, morphology and differential diagnosis of the globular-shaped cleft in the infrapatellar fat pad of the knee on MRI and cadaver dissections. Eur Radiol. 2002;12(1):90–3.

    CAS  PubMed  Google Scholar 

  84. Clockaerts S, et al. The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review. Osteoarthritis Cartilage. 2010;18(7):876–82.

    CAS  PubMed  Google Scholar 

  85. Ioan-Facsinay A, Kloppenburg M. An emerging player in knee osteoarthritis: the infrapatellar fat pad. Arthritis Res Ther. 2013;15(6):225.

    PubMed Central  PubMed  Google Scholar 

  86. Smillie IS. Diseases of the knee joint. 2nd ed. Edinburgh/New York: Churchill Livingstone; 1980.

    Google Scholar 

  87. Fain JN. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm. 2006;74:443–77.

    CAS  PubMed  Google Scholar 

  88. Ushiyama T, et al. Cytokine production in the infrapatellar fat pad: another source of cytokines in knee synovial fluids. Ann Rheum Dis. 2003;62(2):108–12.

    PubMed Central  CAS  PubMed  Google Scholar 

  89. Bohnsack M, et al. Distribution of substance-P nerves inside the infrapatellar fat pad and the adjacent synovial tissue: a neurohistological approach to anterior knee pain syndrome. Arch Orthop Trauma Surg. 2005;125(9):592–7.

    PubMed  Google Scholar 

  90. Lehner B, et al. Preponderance of sensory versus sympathetic nerve fibers and increased cellularity in the infrapatellar fat pad in anterior knee pain patients after primary arthroplasty. J Orthop Res. 2008;26(3):342–50.

    PubMed  Google Scholar 

  91. Klein-Wieringa IR, et al. The infrapatellar fat pad of patients with osteoarthritis has an inflammatory phenotype. Ann Rheum Dis. 2011;70(5):851–7.

    CAS  PubMed  Google Scholar 

  92. Witonski D, et al. Increased interleukin 6 and tumour necrosis factor alpha expression in the infrapatellar fat pad of the knee joint with the anterior knee pain syndrome: a preliminary report. Pol J Pathol. 2010;61(4):213–8.

    PubMed  Google Scholar 

  93. Clements KM, et al. Cellular and histopathological changes in the infrapatellar fat pad in the monoiodoacetate model of osteoarthritis pain. Osteoarthritis Cartilage. 2009;17(6):805–12.

    CAS  PubMed  Google Scholar 

  94. Abbink JJ, et al. Predominant role of neutrophils in the inactivation of alpha 2-macroglobulin in arthritic joints. Arthritis Rheum. 1991;34(9):1139–50.

    CAS  PubMed  Google Scholar 

  95. Tetlow LC, Woolley DE. Effect of histamine on the production of matrix metalloproteinases-1, −3, −8 and −13, and TNFalpha and PGE(2) by human articular chondrocytes and synovial fibroblasts in vitro: a comparative study. Virchows Arch. 2004;445(5):485–90.

    CAS  PubMed  Google Scholar 

  96. Jedrzejczyk T, et al. The infrapatellar adipose body in humans of various age groups. Folia Morphol (Warsz). 1996;55(1):51–5.

    CAS  Google Scholar 

  97. Sakkas LI, Platsoucas CD. The role of T cells in the pathogenesis of osteoarthritis. Arthritis Rheum. 2007;56(2):409–24.

    PubMed  Google Scholar 

  98. Dumond H, et al. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 2003;48(11):3118–29.

    CAS  PubMed  Google Scholar 

  99. Lago R, et al. A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes. Osteoarthritis Cartilage. 2008;16(9):1101–9.

    CAS  PubMed  Google Scholar 

  100. Toussirot E, Streit G, Wendling D. The contribution of adipose tissue and adipokines to inflammation in joint diseases. Curr Med Chem. 2007;14(10):1095–100.

    CAS  PubMed  Google Scholar 

  101. Iliopoulos D, Malizos KN, Tsezou A. Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic chondrocytes: possible molecular target for osteoarthritis therapeutic intervention. Ann Rheum Dis. 2007;66(12):1616–21.

    PubMed Central  CAS  PubMed  Google Scholar 

  102. Presle N, et al. Differential distribution of adipokines between serum and synovial fluid in patients with osteoarthritis. Contribution of joint tissues to their articular production. Osteoarthritis Cartilage. 2006;14(7):690–5.

    CAS  PubMed  Google Scholar 

  103. Koskinen A, et al. Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients. Clin Exp Rheumatol. 2011;29(1):57–64.

    PubMed  Google Scholar 

  104. Matarese G, Leiter EH, La Cava A. Leptin in autoimmunity: many questions, some answers. Tissue Antigens. 2007;70(2):87–95.

    CAS  PubMed  Google Scholar 

  105. Fasshauer M, Paschke R, Stumvoll M. Adiponectin, obesity, and cardiovascular disease. Biochimie. 2004;86(11):779–84.

    CAS  PubMed  Google Scholar 

  106. Gomez R, et al. Adipokines in the skeleton: influence on cartilage function and joint degenerative diseases. J Mol Endocrinol. 2009;43(1):11–8.

    CAS  PubMed  Google Scholar 

  107. Ehling A, et al. The potential of adiponectin in driving arthritis. J Immunol. 2006;176(7):4468–78.

    CAS  PubMed  Google Scholar 

  108. Tang CH, et al. Adiponectin enhances IL-6 production in human synovial fibroblast via an AdipoR1 receptor, AMPK, p38, and NF-kappa B pathway. J Immunol. 2007;179(8):5483–92.

    CAS  PubMed  Google Scholar 

  109. Lotz M, Loeser RF. Effects of aging on articular cartilage homeostasis. Bone. 2012;51(2):241–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  110. Guilak F. Biomechanical factors in osteoarthritis. Best Pract Res Clin Rheumatol. 2011;25(6):815–23.

    PubMed Central  PubMed  Google Scholar 

  111. Sharma AR, et al. Interplay between cartilage and subchondral bone contributing to pathogenesis of osteoarthritis. Int J Mol Sci. 2013;14(10):19805–30.

    PubMed Central  PubMed  Google Scholar 

  112. Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone. 2012;51(2):249–57.

    PubMed Central  CAS  PubMed  Google Scholar 

  113. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 2013;21(1):16–21.

    CAS  PubMed  Google Scholar 

  114. Kean WF, Kean R, Buchanan WW. Osteoarthritis: symptoms, signs and source of pain. Inflammopharmacology. 2004;12(1):3–31.

    CAS  PubMed  Google Scholar 

  115. Bertrand J, et al. Molecular mechanisms of cartilage remodelling in osteoarthritis. Int J Biochem Cell Biol. 2010;42(10):1594–601.

    CAS  PubMed  Google Scholar 

  116. García-Carvajal ZY, et al. Cartilage tissue engineering: the role of extracellular matrix (ECM) and novel strategies. 2013. Regenerative Medicine and Tissue Engineering, Prof. Jose A. Andrades (Ed.), ISBN: 978-953-51-1108-5, InTech, DOI: 10.5772/55917.

    Google Scholar 

  117. Bank RA, et al. A simplified measurement of degraded collagen in tissues: application in healthy, fibrillated and osteoarthritic cartilage. Matrix Biol. 1997;16(5):233–43.

    CAS  PubMed  Google Scholar 

  118. Dodge GR, Poole AR. Immunohistochemical detection and immunochemical analysis of type II collagen degradation in human normal, rheumatoid, and osteoarthritic articular cartilages and in explants of bovine articular cartilage cultured with interleukin 1. J Clin Invest. 1989;83(2):647–61.

    PubMed Central  CAS  PubMed  Google Scholar 

  119. Aigner T, McKenna L. Molecular pathology and pathobiology of osteoarthritic cartilage. Cell Mol Life Sci. 2002;59(1):5–18.

    CAS  PubMed  Google Scholar 

  120. Pearle AD, Warren RF, Rodeo SA. Basic science of articular cartilage and osteoarthritis. Clin Sports Med. 2005;24(1):1–12.

    PubMed  Google Scholar 

  121. Ehrlich MG, et al. The role of proteases in the pathogenesis of osteoarthritis. J Rheumatol. 1987;14 Spec No:30–2.

    CAS  PubMed  Google Scholar 

  122. Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol. 2010;6(11):625–35.

    CAS  PubMed  Google Scholar 

  123. Pearle AD, et al. Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthritis Cartilage. 2007;15(5):516–23.

    CAS  PubMed  Google Scholar 

  124. Sharif M, et al. Increased serum C reactive protein may reflect events that precede radiographic progression in osteoarthritis of the knee. Ann Rheum Dis. 2000;59(1):71–4.

    PubMed Central  CAS  PubMed  Google Scholar 

  125. Spector TD, et al. Low-level increases in serum C-reactive protein are present in early osteoarthritis of the knee and predict progressive disease. Arthritis Rheum. 1997;40(4):723–7.

    CAS  PubMed  Google Scholar 

  126. Sturmer T, et al. Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein. Ann Rheum Dis. 2004;63(2):200–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  127. Jordan JM. Cartilage oligomeric matrix protein as a marker of osteoarthritis. J Rheumatol Suppl. 2004;70:45–9.

    CAS  PubMed  Google Scholar 

  128. Lohmander LS, Saxne T, Heinegard DK. Release of cartilage oligomeric matrix protein (COMP) into joint fluid after knee injury and in osteoarthritis. Ann Rheum Dis. 1994;53(1):8–13.

    PubMed Central  CAS  PubMed  Google Scholar 

  129. Haleem-Smith H, et al. Cartilage oligomeric matrix protein enhances matrix assembly during chondrogenesis of human mesenchymal stem cells. J Cell Biochem. 2012;113(4):1245–52.

    PubMed Central  CAS  PubMed  Google Scholar 

  130. Halász K, et al. COMP acts as a catalyst in collagen fibrillogenesis. J Biol Chem. 2007;282(43):31166–73.

    PubMed  Google Scholar 

  131. Zivanovic S, et al. Cartilage oligomeric matrix protein – inflammation biomarker in knee osteoarthritis. Bosn J Basic Med Sci. 2011;11(1):27–32.

    PubMed Central  CAS  PubMed  Google Scholar 

  132. Stolz M, et al. Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy. Nat Nanotechnol. 2009;4(3):186–92.

    CAS  PubMed  Google Scholar 

  133. Cohen-Solal M, Funck-Brentano T, Hay E. Animal models of osteoarthritis for the understanding of the bone contribution. Bonekey Rep. 2013;2:422.

    PubMed Central  PubMed  Google Scholar 

  134. Bendele AM. Animal models of osteoarthritis. J Musculoskelet Neuronal Interact. 2001;1(4):363–76.

    CAS  PubMed  Google Scholar 

  135. Piccinini AM, Midwood KS. DAMPening inflammation by modulating TLR signalling. Mediators Inflamm. 2010;2010:672395.

    PubMed Central  PubMed  Google Scholar 

  136. Janeway CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197.

    CAS  PubMed  Google Scholar 

  137. Scanzello CR, Plaas A, Crow MK. Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound? Curr Opin Rheumatol. 2008;20(5):565.

    CAS  PubMed  Google Scholar 

  138. Kim HA, et al. The catabolic pathway mediated by Toll‐like receptors in human osteoarthritic chondrocytes. Arthritis Rheum. 2006;54(7):2152–63.

    CAS  PubMed  Google Scholar 

  139. Belcher C, et al. Synovial fluid chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in arthritic and normal knees. Ann Rheum Dis. 1997;56(5):299.

    PubMed Central  CAS  PubMed  Google Scholar 

  140. Scheibner KA, et al. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J Immunol. 2006;177(2):1272.

    CAS  PubMed  Google Scholar 

  141. Taylor KR, et al. Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J Biol Chem. 2004;279(17):17079.

    CAS  PubMed  Google Scholar 

  142. Chevalier X, et al. Presence of ED-A containing fibronectin in human articular cartilage from patients with osteoarthritis and rheumatoid arthritis. J Rheumatol. 1996;23(6):1022–30.

    CAS  PubMed  Google Scholar 

  143. Chevalier X, et al. Tenascin distribution in articular cartilage from normal subjects and from patients with osteoarthritis and rheumatoid arthritis. Arthritis Rheum. 1994;37(7):1013–22.

    CAS  PubMed  Google Scholar 

  144. Midwood K, et al. Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat Med. 2009;15(7):774–80.

    CAS  PubMed  Google Scholar 

  145. Cs-Szabo G, et al. Large and small proteoglycans of osteoarthritic and rheumatoid articular cartilage. Arthritis Rheum. 1995;38(5):660–8.

    CAS  PubMed  Google Scholar 

  146. Schaefer L, et al. The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. J Clin Invest. 2005;115(8):2223–33.

    PubMed Central  CAS  PubMed  Google Scholar 

  147. Liu-Bryan R, Terkeltaub R. Chondrocyte innate immune myeloid differentiation factor 88-dependent signaling drives procatabolic effects of the endogenous Toll-like receptor 2/Toll-like receptor 4 ligands low molecular weight hyaluronan and high mobility group box chromosomal protein 1 in mice. Arthritis Rheum. 2010;62(7):2004–12.

    PubMed Central  PubMed  Google Scholar 

  148. Akira S. Toll-like receptor signaling. J Biol Chem. 2003;278(40):38105.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  150. Mankin HJ, Thrasher AZ. Water content and binding in normal and osteoarthritic human cartilage. J Bone Joint Surg Am. 1975;57(1):76–80.

    CAS  PubMed  Google Scholar 

  151. Stockwell RA. Cartilage failure in osteoarthritis: relevance of normal structure and function. A review. Clin Anat. 1991;4:161–91.

    Google Scholar 

  152. Radin EL, Rose RM. Role of subchondral bone in the initiation and progression of cartilage damage. Clin Orthop Relat Res. 1986;213:34.

    PubMed  Google Scholar 

  153. Neogi T, et al. Cartilage loss occurs in the same subregions as subchondral bone attrition: a within-knee subregion-matched approach from the Multicenter Osteoarthritis study. Arthritis Rheum. 2009;61(11):1539–44.

    PubMed Central  CAS  PubMed  Google Scholar 

  154. Intema F, et al. In early OA, thinning of the subchondral plate is directly related to cartilage damage: results from a canine ACLT-meniscectomy model. Osteoarthritis Cartilage. 2010;18(5):691–8.

    CAS  PubMed  Google Scholar 

  155. Burr DB, Radin EL. Microfractures and microcracks in subchondral bone: are they relevant to osteoarthrosis? Rheum Dis Clin North Am. 2003;29(4):675–85.

    PubMed  Google Scholar 

  156. McErlain DD, et al. An in vivo investigation of the initiation and progression of subchondral cysts in a rodent model of secondary osteoarthritis. Arthritis Res Ther. 2012;14(1):R26.

    PubMed Central  PubMed  Google Scholar 

  157. Pfander D, Rahmanzadeh R, Scheller EE. Presence and distribution of collagen II, collagen I, fibronectin, and tenascin in rabbit normal and osteoarthritic cartilage. J Rheumatol. 1999;26(2):386–94.

    CAS  PubMed  Google Scholar 

  158. Lee DA, Bentley G, Archer CW. The control of cell division in articular chondrocytes. Osteoarthritis Cartilage. 1993;1(2):137–46.

    CAS  PubMed  Google Scholar 

  159. Goldring MB. The role of cytokines as inflammatory mediators in osteoarthritis: lessons from animal models. Connect Tissue Res. 1999;40(1):1–11.

    CAS  PubMed  Google Scholar 

  160. Sandell LJ, Aigner T. Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Res. 2001;3(2):107–13.

    PubMed Central  CAS  PubMed  Google Scholar 

  161. Fortier L, et al. The role of growth factors in cartilage repair. Clin Orthop Relat Res. 2011;469(10):2706–15.

    PubMed Central  PubMed  Google Scholar 

  162. Rothwell AG, Bentley G. Chondrocyte multiplication in osteoarthritic articular cartilage. J Bone Joint Surg Br. 1973;55(3):588–94.

    CAS  PubMed  Google Scholar 

  163. Kirsch T, Swoboda B, Nah HD. Activation of annexin II and V expression, terminal differentiation, mineralization and apoptosis in human osteoarthritic cartilage. Osteoarthritis Cartilage. 2000;8(4):294–302.

    CAS  PubMed  Google Scholar 

  164. Mahjoub M, Berenbaum F, Houard X. Why subchondral bone in osteoarthritis? The importance of the cartilage bone interface in osteoarthritis. Osteoporos Int. 2012;23 Suppl 8:S841–6.

    PubMed  Google Scholar 

  165. Fuerst M, et al. Calcification of articular cartilage in human osteoarthritis. Arthritis Rheum. 2009;60(9):2694–703.

    CAS  PubMed  Google Scholar 

  166. Hattori T, et al. SOX9 is a major negative regulator of cartilage vascularization, bone marrow formation and endochondral ossification. Development. 2010;137(6):901–11.

    CAS  PubMed  Google Scholar 

  167. Lefebvre V, Behringer RR, de Crombrugghe B. L-Sox5, Sox6 and Sox9 control essential steps of the chondrocyte differentiation pathway. Osteoarthritis Cartilage. 2001;9 Suppl 1:S69–75.

    Google Scholar 

  168. Goldring MB, Tsuchimochi K, Ijiri K. The control of chondrogenesis. J Cell Biochem. 2006;97(1):33–44.

    CAS  PubMed  Google Scholar 

  169. Kamekura S, et al. Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability. Arthritis Rheum. 2006;54(8):2462–70.

    CAS  PubMed  Google Scholar 

  170. Goldring SR. Role of bone in osteoarthritis pathogenesis. Med Clin North Am. 2009;93(1):25–35, xv.

    PubMed  Google Scholar 

  171. von der Mark K, et al. Type X collagen synthesis in human osteoarthritic cartilage. Indication of chondrocyte hypertrophy. Arthritis Rheum. 1992;35(7):806–11.

    PubMed  Google Scholar 

  172. Hoyland JA, et al. Distribution of type X collagen mRNA in normal and osteoarthritic human cartilage. Bone Miner. 1991;15(2):151–63.

    CAS  PubMed  Google Scholar 

  173. Oegema Jr TR, et al. The interaction of the zone of calcified cartilage and subchondral bone in osteoarthritis. Microsc Res Tech. 1997;37(4):324–32.

    PubMed  Google Scholar 

  174. Lane LB, Bullough PG. Age-related changes in the thickness of the calcified zone and the number of tidemarks in adult human articular cartilage. J Bone Joint Surg Br. 1980;62(3):372–5.

    CAS  PubMed  Google Scholar 

  175. Walsh DA, et al. Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis. Osteoarthritis Cartilage. 2007;15(7):743–51.

    CAS  PubMed  Google Scholar 

  176. Cox LG, et al. Alterations to the subchondral bone architecture during osteoarthritis: bone adaptation vs endochondral bone formation. Osteoarthritis Cartilage. 2013;21(2):331–8.

    CAS  PubMed  Google Scholar 

  177. Pfander D, et al. Vascular endothelial growth factor in articular cartilage of healthy and osteoarthritic human knee joints. Ann Rheum Dis. 2001;60(11):1070–3.

    PubMed Central  CAS  PubMed  Google Scholar 

  178. Walsh DA, et al. Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis. Rheumatology (Oxford). 2010;49(10):1852–61.

    CAS  Google Scholar 

  179. Karsdal MA, et al. Should subchondral bone turnover be targeted when treating osteoarthritis? Osteoarthritis Cartilage. 2008;16(6):638–46.

    CAS  PubMed  Google Scholar 

  180. Lorenz H, Richter W. Osteoarthritis: cellular and molecular changes in degenerating cartilage. Prog Histochem Cytochem. 2006;40(3):135–63.

    CAS  PubMed  Google Scholar 

  181. Grogan SP, D’Lima DD. Joint aging and chondrocyte cell death. Int J Clin Rheumtol. 2010;5(2):199–214.

    PubMed Central  PubMed  Google Scholar 

  182. Kuhn K, et al. Cell death in cartilage. Osteoarthritis Cartilage. 2004;12(1):1–16.

    CAS  PubMed  Google Scholar 

  183. Kim HA, Blanco FJ. Cell death and apoptosis in osteoarthritic cartilage. Curr Drug Targets. 2007;8(2):333–45.

    CAS  PubMed  Google Scholar 

  184. Temple MM, et al. Age- and site-associated biomechanical weakening of human articular cartilage of the femoral condyle. Osteoarthritis Cartilage. 2007;15(9):1042–52.

    CAS  PubMed  Google Scholar 

  185. Blanco FJ, et al. Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology. Arthritis Rheum. 1998;41(2):284–9.

    CAS  PubMed  Google Scholar 

  186. Taylor RC, Cullen SP, Martin SJ. Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol. 2008;9(3):231–41.

    CAS  PubMed  Google Scholar 

  187. Wajant H. The Fas signaling pathway: more than a paradigm. Science. 2002;296(5573):1635–6.

    CAS  PubMed  Google Scholar 

  188. Kim J, et al. Mitochondrial DNA damage is involved in apoptosis caused by pro-inflammatory cytokines in human OA chondrocytes. Osteoarthritis Cartilage. 2010;18(3):424–32.

    CAS  PubMed  Google Scholar 

  189. Thornberry NA, Lazebnik Y. Caspases: enemies within. Science. 1998;281(5381):1312–6.

    CAS  PubMed  Google Scholar 

  190. Krysko DV, et al. Apoptosis and necrosis: detection, discrimination and phagocytosis. Methods. 2008;44(3):205–21.

    CAS  PubMed  Google Scholar 

  191. Hashimoto S, et al. Fas/Fas ligand expression and induction of apoptosis in chondrocytes. Arthritis Rheum. 1997;40(10):1749–55.

    CAS  PubMed  Google Scholar 

  192. Shakibaei M, Csaki C, Mobasheri A. Diverse roles of integrin receptors in articular cartilage. Adv Anat Embryol Cell Biol. 2008;197:1–60.

    CAS  PubMed  Google Scholar 

  193. Thomas CM, et al. Chondrocyte death by apoptosis is associated with the initiation and severity of articular cartilage degradation. Int J Rheum Dis. 2011;14(2):191–8.

    PubMed  Google Scholar 

  194. Hashimoto S, et al. Chondrocyte-derived apoptotic bodies and calcification of articular cartilage. Proc Natl Acad Sci U S A. 1998;95(6):3094–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  195. Mobasheri A. Role of chondrocyte death and hypocellularity in ageing human articular cartilage and the pathogenesis of osteoarthritis. Med Hypotheses. 2002;58(3):193–7.

    CAS  PubMed  Google Scholar 

  196. Wu GJ, et al. Nitric oxide from both exogenous and endogenous sources activates mitochondria-dependent events and induces insults to human chondrocytes. J Cell Biochem. 2007;101(6):1520–31.

    CAS  PubMed  Google Scholar 

  197. Min BH, et al. Effects of ageing and arthritic disease on nitric oxide production by human articular chondrocytes. Exp Mol Med. 2001;33(4):299–302.

    CAS  PubMed  Google Scholar 

  198. Lopez-Armada MJ, et al. Cytokines, tumor necrosis factor-alpha and interleukin-1beta, differentially regulate apoptosis in osteoarthritis cultured human chondrocytes. Osteoarthritis Cartilage. 2006;14(7):660–9.

    CAS  PubMed  Google Scholar 

  199. Carames B, et al. Differential effects of tumor necrosis factor-alpha and interleukin-1beta on cell death in human articular chondrocytes. Osteoarthritis Cartilage. 2008;16(6):715–22.

    CAS  PubMed  Google Scholar 

  200. Holmstrom KM, Finkel T. Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat Rev Mol Cell Biol. 2014;15(6):411–21.

    CAS  PubMed  Google Scholar 

  201. Aigner T, et al. 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(6):1304–12.

    CAS  PubMed  Google Scholar 

  202. Meachim G, Collins DH. Cell counts of normal and osteo-arthritic articular cartilage in relation to the uptake of sulphate ((35)SO(4)) in vitro. Ann Rheum Dis. 1962;21(1):45–50.

    PubMed Central  CAS  PubMed  Google Scholar 

  203. Terman A, et al. Mitochondrial turnover and aging of long-lived postmitotic cells: the mitochondrial–lysosomal axis theory of aging. Antioxid Redox Signal. 2010;12(4):503–35.

    PubMed Central  CAS  PubMed  Google Scholar 

  204. Lotz MK, Carames B. Autophagy and cartilage homeostasis mechanisms in joint health, aging and OA. Nat Rev Rheumatol. 2011;7(10):579–87.

    PubMed Central  CAS  PubMed  Google Scholar 

  205. Mizushima N. Physiological functions of autophagy. Curr Top Microbiol Immunol. 2009;335:71–84.

    CAS  PubMed  Google Scholar 

  206. He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 2009;43:67–93.

    PubMed Central  CAS  PubMed  Google Scholar 

  207. Hara T, et al. FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J Cell Biol. 2008;181(3):497–510.

    PubMed Central  CAS  PubMed  Google Scholar 

  208. Kang R, et al. The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ. 2011;18(4):571–80.

    PubMed Central  CAS  PubMed  Google Scholar 

  209. Tanida I, Ueno T, Kominami E. LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol. 2004;36(12):2503–18.

    CAS  PubMed  Google Scholar 

  210. Cuervo AM, Dice JF. Age-related decline in chaperone-mediated autophagy. J Biol Chem. 2000;275(40):31505–13.

    CAS  PubMed  Google Scholar 

  211. Carames B, et al. Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis. Arthritis Rheum. 2010;62(3):791–801.

    PubMed Central  CAS  PubMed  Google Scholar 

  212. Marino G, et al. Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol. 2014;15(2):81–94.

    PubMed Central  CAS  PubMed  Google Scholar 

  213. Almonte-Becerril M, et al. Cell death of chondrocytes is a combination between apoptosis and autophagy during the pathogenesis of Osteoarthritis within an experimental model. Apoptosis. 2010;15(5):631–8.

    CAS  PubMed  Google Scholar 

  214. Hayflick L. Intracellular determinants of cell aging. Mech Ageing Dev. 1984;28(2–3):177–85.

    CAS  PubMed  Google Scholar 

  215. Muller M. Cellular senescence: molecular mechanisms, in vivo significance, and redox considerations. Antioxid Redox Signal. 2009;11(1):59–98.

    CAS  PubMed  Google Scholar 

  216. Goyns MH. Genes, telomeres and mammalian ageing. Mech Ageing Dev. 2002;123(7):791–9.

    CAS  PubMed  Google Scholar 

  217. Lundblad V. Telomere end processing: unexpected complexity at the end game. Genes Dev. 2012;26(11):1123–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  218. Watson JD. Origin of concatemeric T7 DNA. Nat New Biol. 1972;239(94):197–201.

    CAS  PubMed  Google Scholar 

  219. Loeser RF. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthritis Cartilage. 2009;17(8):971–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  220. Itahana K, Campisi J, Dimri GP. Mechanisms of cellular senescence in human and mouse cells. Biogerontology. 2004;5(1):1–10.

    CAS  PubMed  Google Scholar 

  221. Campisi J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell. 2005;120(4):513–22.

    CAS  PubMed  Google Scholar 

  222. Yudoh K, et al. Potential involvement of oxidative stress in cartilage senescence and development of osteoarthritis: oxidative stress induces chondrocyte telomere instability and downregulation of chondrocyte function. Arthritis Res Ther. 2005;7(2):R380–91.

    PubMed Central  CAS  PubMed  Google Scholar 

  223. Martin JA, Buckwalter JA. Telomere erosion and senescence in human articular cartilage chondrocytes. J Gerontol A Biol Sci Med Sci. 2001;56(4):B172–9.

    CAS  PubMed  Google Scholar 

  224. Martin JA, Buckwalter JA. The role of chondrocyte senescence in the pathogenesis of osteoarthritis and in limiting cartilage repair. J Bone Joint Surg Am. 2003;85-A Suppl 2:106–10.

    PubMed  Google Scholar 

  225. Price JS, et al. The role of chondrocyte senescence in osteoarthritis. Aging Cell. 2002;1(1):57–65.

    CAS  PubMed  Google Scholar 

  226. Dai SM, et al. Catabolic stress induces features of chondrocyte senescence through overexpression of caveolin 1: possible involvement of caveolin 1-induced down-regulation of articular chondrocytes in the pathogenesis of osteoarthritis. Arthritis Rheum. 2006;54(3):818–31.

    CAS  PubMed  Google Scholar 

  227. Zhang R, Adams PD. Heterochromatin and its relationship to cell senescence and cancer therapy. Cell Cycle. 2007;6(7):784–9.

    CAS  PubMed  Google Scholar 

  228. Freund A, et al. Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med. 2010;16(5):238–46.

    PubMed Central  CAS  PubMed  Google Scholar 

  229. Campisi J, d’Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007;8(9):729–40.

    CAS  PubMed  Google Scholar 

  230. Acosta JC, et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol. 2013;15(8):978–90.

    PubMed Central  CAS  PubMed  Google Scholar 

  231. Tchkonia T, et al. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Invest. 2013;123(3):966–72.

    PubMed Central  CAS  PubMed  Google Scholar 

  232. Zhu Y, et al. Cellular senescence and the senescent secretory phenotype in age-related chronic diseases. Curr Opin Clin Nutr Metab Care. 2014;17(4):324–8.

    CAS  PubMed  Google Scholar 

  233. Guerne P-A, et al. Growth factor responsiveness of human articular chondrocytes in aging and development. Arthritis Rheum. 1995;38(7):960–8.

    CAS  PubMed  Google Scholar 

  234. Iqbal J, et al. Age-related effects of TGF-beta on proteoglycan synthesis in equine articular cartilage. Biochem Biophys Res Commun. 2000;274(2):467.

    CAS  PubMed  Google Scholar 

  235. Martin JA, Ellerbroek SM, Buckwalter JA. Age-related decline in chondrocyte response to insulin-like growth factor-I: the role of growth factor binding proteins. J Orthop Res. 1997;15(4):491–8.

    CAS  PubMed  Google Scholar 

  236. Loeser RF, et al. Reduction in the chondrocyte response to insulin-like growth factor 1 in aging and osteoarthritis: studies in a non-human primate model of naturally occurring disease. Arthritis Rheum. 2000;43(9):2110–20.

    CAS  PubMed  Google Scholar 

  237. Bobacz K, et al. Expression of bone morphogenetic protein 6 in healthy and osteoarthritic human articular chondrocytes and stimulation of matrix synthesis in vitro. Arthritis Rheum. 2003;48(9):2501–8.

    CAS  PubMed  Google Scholar 

  238. Tran-Khanh N, et al. Aged bovine chondrocytes display a diminished capacity to produce a collagen-rich, mechanically functional cartilage extracellular matrix. J Orthop Res. 2005;23(6):1354–62.

    CAS  PubMed  Google Scholar 

  239. Loeser RF, Shanker G. Autocrine stimulation by insulin-like growth factor 1 and insulin-like growth factor 2 mediates chondrocyte survival in vitro. Arthritis Rheum. 2000;43(7):1552–9.

    CAS  PubMed  Google Scholar 

  240. Studer RK, et al. Nitric oxide inhibits chondrocyte response to IGF-I: inhibition of IGF-IRbeta tyrosine phosphorylation. Am J Physiol Cell Physiol. 2000;279(4):C961–9.

    CAS  PubMed  Google Scholar 

  241. Blaney Davidson EN, et al. Reduced transforming growth factor-beta signaling in cartilage of old mice: role in impaired repair capacity. Arthritis Res Ther. 2005;7(6):R1338–47.

    PubMed Central  CAS  PubMed  Google Scholar 

  242. Chubinskaya S, et al. Age-related changes in cartilage endogenous osteogenic protein-1 (OP-1). Biochim Biophys Acta. 2002;1588(2):126–34.

    CAS  PubMed  Google Scholar 

  243. Loeser RF, et al. Methylation of the OP-1 promoter: potential role in the age-related decline in OP-1 expression in cartilage. Osteoarthritis Cartilage. 2009;17(4):513–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  244. Carlo Jr MD, Loeser RF. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum. 2003;48(12):3419–30.

    PubMed  Google Scholar 

  245. Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature. 2000;408(6809):239–47.

    CAS  PubMed  Google Scholar 

  246. Jallali N, et al. Vulnerability to ROS-induced cell death in ageing articular cartilage: the role of antioxidant enzyme activity. Osteoarthritis Cartilage. 2005;13(7):614–22.

    CAS  PubMed  Google Scholar 

  247. Grishko VI, et al. Diminished mitochondrial DNA integrity and repair capacity in OA chondrocytes. Osteoarthritis Cartilage. 2009;17(1):107–13.

    PubMed Central  CAS  PubMed  Google Scholar 

  248. Lo YY, Cruz TF. Involvement of reactive oxygen species in cytokine and growth factor induction of c-fos expression in chondrocytes. J Biol Chem. 1995;270(20):11727–30.

    CAS  PubMed  Google Scholar 

  249. Jallali N, et al. Modulation of intracellular reactive oxygen species level in chondrocytes by IGF-1, FGF, and TGF-beta1. Connect Tissue Res. 2007;48(3):149–58.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Genetics and Development, The Toronto Western Research Institute, The University Health Network (UHN), 60 Leonard Avenue, Toronto, ON, Canada, M5T 2S8

    Mohit Kapoor PhD

  2. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Mohit Kapoor PhD

  3. Division of Orthopaedics, Toronto Western Hospital, Toronto, ON, Canada

    Mohit Kapoor PhD

Authors
  1. Mohit Kapoor PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mohit Kapoor PhD .

Editor information

Editors and Affiliations

  1. Division of Genetics and Development, Toronto Western Research Institute, University Health Network and Department of Surgery, University of Toronto, Toronto, Ontario, Canada

    Mohit Kapoor

  2. Division of Orthopaedics, Toronto Western Hospital, Toronto, Ontario, Canada

    Nizar N. Mahomed

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Kapoor, M. (2015). Pathogenesis of Osteoarthritis. In: Kapoor, M., Mahomed, N. (eds) Osteoarthritis. Adis, Cham. https://doi.org/10.1007/978-3-319-19560-5_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-19560-5_1

  • Publisher Name: Adis, Cham

  • Print ISBN: 978-3-319-19559-9

  • Online ISBN: 978-3-319-19560-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation