Chondrocyte Hypertrophy and Apoptosis at the Cartilage-Bone Interface

  • Irving M. Shapiro
  • Christopher S. Adams
  • Vickram Srinivas
  • Theresa A. Freeman
Part of the Topics in Bone Biology book series (TBB, volume 4)


Articular Cartilage Osmotic Pressure Growth Plate Primary Cilium Articular Chondrocytes 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adams CS, Horton WE (1998) Chondrocyte apoptosis increases with age in the articular cartilage of adult animals. Anat Rec 250:418–425.PubMedGoogle Scholar
  2. 2.
    Aigner T, Hemmel M, Neureiter D, Gebhard PM, Zeiler G, Kirchner T, and McKenna L (2001) 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 44:1304–1312.PubMedGoogle Scholar
  3. 3.
    Aigner T, Rose J, Martin J, and Buckwalter J (2004) Aging theories of primary osteoarthritis: from epidemiology to molecular biology. Rejuven Res 7:134–145.Google Scholar
  4. 4.
    Alberts B (1998) The cell as a collection of protein machines: preparing the next generation of molecular biologists. Cell 92:291–294.PubMedGoogle Scholar
  5. 5.
    Bank RA, Soudry M, Maroudas A, Mizrahi J, and Tekoppele JM (2000) The increased swelling and instantaneous deformation of osteoarthritic cartilage is highly correlated with collagen degradation. Arthritis Rheum 43:2202–2210.PubMedGoogle Scholar
  6. 6.
    Barnett CH, Cochrane W, Palfrey AJ (1963) Age changes in articular cartilage of rabbits. Ann Rheum Dis 22:389–400.PubMedGoogle Scholar
  7. 7.
    Bjorkstrom S and Goldie IF (1980) A study of the arterial supply of the patella in the normal state, in chondromalacia patellae and in osteoarthrosis. Acta Orthop Scand 51:63–70.PubMedGoogle Scholar
  8. 8.
    Blanco FJ, Guitan R, Vázquez-Martul E, de Toro FJ, and Galdo F (1998) Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology. Arthritis Rheum 41:284–289.PubMedGoogle Scholar
  9. 9.
    Blanco FJ, Ochs RL, Schwarz H, and Lotz M (1995) Chondrocyte apoptosis induced by nitric oxide. Am J Pathol 146:75–85.PubMedGoogle Scholar
  10. 10.
    Boyde A, Firth EC Articular calcified cartilage canals in the third metacarpal bone of 2-year-old thoroughbred racehorses. J Anat 205:491–500.Google Scholar
  11. 11.
    Brandt KD, Lohmander LS, Doherty M (1998) Pathogenesis of osteoarthritis—introduction. In: Brandt KD, Doherty M, Lohmander LS, eds. Osteoarthritis. New York: Oxford University Press, pp. 70–74.Google Scholar
  12. 12.
    Bras M, Queenan B, Susin SA (2005) Programmed cell death via mitochondria: different modes of dying. Biochemistry-Russia 70:231–239.Google Scholar
  13. 13.
    Budovskaya YV, Stephan JS, Reggiori F, Klionsky DJ, and Herman PK (2004) The Ras/cAMP-dependent protein kinase signaling pathway regulates an early step of the autophagy process in Saccharomyces cerevisiae. J Biol Chem 279:20663–20671.PubMedGoogle Scholar
  14. 14.
    Bush PG, Hall AC (2001) The osmotic sensitivity of isolated and in situ bovine articular chondrocytes. J Orthop Res 19:768–778.PubMedGoogle Scholar
  15. 15.
    Bush PG, Hall AC (2003) The volume and morphology of chondrocytes within non-degenerate and degenerate human articular cartilage. Osteoarthritis Cartilage 11:242–251.PubMedGoogle Scholar
  16. 16.
    Bush PG, Hall AC (2005) Passive osmotic properties of in situ human articular chondrocytes within non-degenerate and degenerate cartilage. J Cell Physiol 204:309–319.PubMedGoogle Scholar
  17. 17.
    Carlo MD Jr, Loeser RF (2003) Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum 48:3419–3430.PubMedGoogle Scholar
  18. 18.
    Clark JM (1990) The structure of vascular channels in the subchondral plate. J Anat 171:105–115.PubMedGoogle Scholar
  19. 19.
    Desai BN, Myers BR, Schreiber SL (2002) FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction. Proc Natl Acad Sci USA 99:4319–4324.PubMedGoogle Scholar
  20. 20.
    Ehrlich MG, Houle MG, Vigliani G, and Mankin HJ (1978) Correlation between articular cartilage collagenase activity and osteoarthritis. Arthritis Rheum 21:761–766.PubMedGoogle Scholar
  21. 21.
    Ellis RJ (2001) Macromolecular crowding: obvious but underappreciated. Trends Biochem Sci 26:597–604.PubMedGoogle Scholar
  22. 22.
    Erenpreisa J, Roach HI (1998) Aberrant death in dark chondrocytes of the avian growth plate. Cell Death Different 5:60–66.Google Scholar
  23. 23.
    Farnum CE, Lee R, O’Hara K, and Urban JPG (2002) Volume increase in growth plate chondrocytes during hypertrophy: the contribution of organic osmolytes. Bone 30:574–581.PubMedGoogle Scholar
  24. 24.
    Fawns HT, Landells JW (1953) Histochemical studies of rheumatic conditions I. Observations on the fine structures of the matrix of normal bone and cartilage. Ann Rheum Dis 12:105–113.PubMedGoogle Scholar
  25. 25.
    Feng L, Balakir R, Precht P, and Horton WE, Jr (1999) Bcl-2 regulates chondrocyte morphology and aggrecan gene expression independent of caspase activation and full apoptosis. J Cell Biochem 74:576–586.PubMedGoogle Scholar
  26. 26.
    Feng L, Precht P, Balakir R, and Horton WE, Jr (1998) Evidence of a direct role for Bcl-2 in the regulation of articular chondrocyte apoptosis under the conditions of serum withdrawal and retinoic acid treatment. J Cell Biochem 71:302–309.PubMedGoogle Scholar
  27. 27.
    Fernandez-Criado C, Martos-Rodriguez A, Santos-Alvarez I, Garcia-Ruiz JP, and Delgado-Baeza E (2004) The fate of chondrocyte in osteoarthritic cartilage of transgenic mice expressing bovine GH*1. Osteoarthritis Cartilage 12:543–551.PubMedGoogle Scholar
  28. 28.
    Gibson G, Wang X, Yang M (2002) The release and activation of TGF-B associated with chondrocyte hypertrophy and apoptosis. In: Shapiro IM, Boyan BD, Anderson HC, eds. The Growth Plate. Amsterdam: IOS Press, pp. 77–93.Google Scholar
  29. 29.
    Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, Ma HL, Flannery CR, Peluso D, Kanki K, Yang Z, Majumdar MK, and Morris EA (2005) Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 434:644–648.PubMedGoogle Scholar
  30. 30.
    Gozuacik D, Kimchi A (2004) Autophagy as a cell death and tumor suppressor mechanism. Oncogene 23:2891–2906.PubMedGoogle Scholar
  31. 31.
    Greisberg J, Bliss M, Terek R (2002) The prevalence of nitric oxide in apoptotic chondrocytes of osteoarthritis. Osteoarthritis Cartilage 10:207–211.PubMedGoogle Scholar
  32. 32.
    Hall AC (1995) Volume-sensitive taurine transport in bovine articular chondrocytes. J Physiol 484:755–766.PubMedGoogle Scholar
  33. 33.
    Hashimoto S, Ochs RL, Komiya S, and Lotz M (1998) Linkage of chondrocyte apoptosis and cartilage degradation in human osteoarthritis. Arthritis Rheum 41:1632–1638.PubMedGoogle Scholar
  34. 34.
    Hashimoto S, Setareh M, Ochs RL, and Lotz M (1997) Fas/Fas ligand expression and induction of apoptosis in chondrocytes. Arthritis Rheum 40:1749–1755.PubMedGoogle Scholar
  35. 35.
    Hashimoto S, Takahashi K, Amiel D, Coutts RD, and Lotz M (1998) Chondrocyte apoptosis and nitric oxide production during experimentally induced osteoarthritis. Arthritis Rheum 41:1266–1274.PubMedGoogle Scholar
  36. 36.
    Hatori M, Klatte KJ, Teixeira CC, and Shapiro IM (1995) End labeling studies of fragmented DNA in the avian growth plate: evidence of apoptosisin terminally differentiated chondrocytes. J Bone Miner Res 10:1960–1968.PubMedGoogle Scholar
  37. 37.
    Heraud F, Heraud A, Harmand MF (2000) Apoptosis in normal and osteoarthritic human articular cartilage. Ann Rheum Dis 59:959–965.PubMedGoogle Scholar
  38. 38.
    Hochberg MC, Lethbridge-Cejku M, Scott WW, Jr, Plato CC, and Tobin JD (1993) Obesity and osteoarthritis of the hands in women. Osteoarthritis Cartilage 1:129–135.PubMedGoogle Scholar
  39. 39.
    Homandberg GA (2001) Cartilage damage by matrix degradation products: fibronectin fragments. Clin Orthop Relat Res 391(suppl):S100–S107.PubMedGoogle Scholar
  40. 40.
    Honda HM, Korge PAV, Weiss JN (2005) Mitochondria and ischemia/reperfusion injury. Ann NY Acad Sci 1047:248–258.PubMedGoogle Scholar
  41. 41.
    Hughes FM, Jr, Evans-Storms RB, Cidlowski JA (1998) Evidence that non-caspase proteases are required for chromatin degradation during apoptosis. Cell Death Differentiation 2:1017–1027.Google Scholar
  42. 42.
    Hughes LC, Archer CW, Gwynn IAP (2005) The ultrastructure of mouse articular cartilage: collagen orientation and implications for tissue functionality. A polarised light and scanning electron microscope study and review. Eur Cells Materials J 9:68–84.Google Scholar
  43. 43.
    Iannone F, De Bari C, Scioscia C, Patella V, and Lapadula G (2005) Increased Bcl-2/p53 ratio in human osteoarthritic cartilage: a possible role in regulation of chondrocyte metabolism. Ann Rheum Dis 64:217–221.PubMedGoogle Scholar
  44. 44.
    Iannone F, Lapadula G (2003) The pathophysiology of osteoarthritis. Aging Clin Exp Res 15:364–372.PubMedGoogle Scholar
  45. 45.
    Imhof H, Breitenseher M, Kainberger F, and Trattnig S (1997) Degenerative joint disease: cartilage or vascular disease? Skel Radiol 26:398–403.Google Scholar
  46. 46.
    Ingber DE (1997) Tensegrity: the architectural basis of cellular mechanotransduction. Annu Rev Physiol 59:575–599.PubMedGoogle Scholar
  47. 47.
    Ingber DE (2003) Tensegrity II. How structural networks influence cellular information processing networks. J Cell Sci 116:1397–1408.PubMedGoogle Scholar
  48. 48.
    Ingber DE (2003) Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci 116:1157–1173.PubMedGoogle Scholar
  49. 49.
    Ishibashi H, Takenoshita Y, Ishibashi K, and Oka M (1995) Age-related changes in the human mandibular condyle: a morphologic, radiologic, and histologic study. J Oral Maxillofac Surg 53:1016–1023.PubMedGoogle Scholar
  50. 50.
    Jacinto E, Hall MN (2003) Tor signalling in bugs, brain and brawn. Nature Rev Mol Cell Biol 4:117–126.Google Scholar
  51. 51.
    Jakab M, Furst J, Gschwentner M, Botta G, Garavaglia ML, Bazzini C, Rodighiero S, Meyer G, Eichmueller S, Woll E, Chwatal S, Ritter M, and Paulmichl M (2002) Mechanisms sensing and modulating signals arising from cell swelling. Cell Physiol Biochem 12:235–258.PubMedGoogle Scholar
  52. 52.
    Jensen CG, Poole CA, McGlashan SR, Marko M, Issa ZI, Vujcich KV, and Bowser SS (2004) Ultrastructural, tomographic and confocal imaging of the chondrocyte primary cilium in situ. Cell Biol Int 28:101–110.PubMedGoogle Scholar
  53. 53.
    Jewell F, Watt I (1996) Arthritis: imaging and therapy. Past, present and future. Radiologe 36:646–656.PubMedGoogle Scholar
  54. 54.
    Kapitonova MY, Mansor O (2003) Ultrastructural changes of the articular cartilage in some arthropathies with special reference to chondrocyte cell death. Malaysian J Pathol 25:15–27.Google Scholar
  55. 55.
    Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26:239–257.PubMedGoogle Scholar
  56. 56.
    Kim HA, Lee YJ, Seong SC, Choe KW, and Song YW (2000) Apoptotic chondrocyte death in human osteoarthritis. J Rheumatol 27:455–462.PubMedGoogle Scholar
  57. 57.
    Kirsch T, Swoboda B, Nah H (2000) Activation of annexin II and V expression, terminal differentiation, mineralization and apoptosis in human osteoarthritic cartilage. Osteoarthritis Cartilage 8:294–302.PubMedGoogle Scholar
  58. 58.
    Klionsky DJ (2005) The molecular machinery of autophagy: unanswered questions. J Cell Sci 118:7–18.PubMedGoogle Scholar
  59. 59.
    Kobayashi K, Mishima H, Hashimoto S, Goomer RS, Harwood FL, Lotz M, Moriya H, and Amiel D (2001) Chondrocyte apoptosis and regional differential expression of nitric oxide in the medial meniscus following partial meniscectomy. J Orthop Res 19:802–808.PubMedGoogle Scholar
  60. 60.
    Kotoulas OB, Kalamidas SA, Kondomerkos DJ (2004) Glycogen autophagy. Microsc Res Tech 64:10–20.PubMedGoogle Scholar
  61. 61.
    Kouri JB, Aguilera JM, Reyes J, Lozoya KA, and Gonzalez S (2000) Apoptotic chondrocytes from osteoarthrotic human articular cartilage and abnormal calcification of subchondral bone. J Rheumatol 27:1005–1019.PubMedGoogle Scholar
  62. 62.
    Kouri-Flores JB, Abbud-Lozoya KA, Roja-Morales L (2002) Kinetics of the ultrastructural changes in apoptotic chondrocytes from an osteoarthrosis rat model: a window of comparison to the cellular mechanism of apoptosis in human chondrocytes. Ultrastruct Pathol 26:33–40.PubMedGoogle Scholar
  63. 63.
    Kraus VB (1997) Pathogenesis and treatment of osteoarthritis. Med Clin North Am 81:85–112.PubMedGoogle Scholar
  64. 64.
    Kundu M, Thompson CB (2005) Macroautophagy versus mitochondrial autophagy: a question of fate? Cell Death Differentiation 12:1484–1489.Google Scholar
  65. 65.
    Lammi MJ, Qu CJ, Laasanen MS, Saarakkala S, Rieppo J, Jurvelin JS, and Toyras J (2004) Undersulfated chondroitin sulfate does not increase in osteoarthritic cartilage. J Rheumatol 31:2449–2453.PubMedGoogle Scholar
  66. 66.
    Lethbridge-Cejku M, Tobin JD, Scott WW, Jr, Reichle R, Plato CC, and Hochberg MC (1994) The relationship of age and gender to prevalence and pattern of radiographic changes of osteoarthritis of the knee: data from Caucasian participants in the Baltimore Longitudinal Study of Aging. Aging (Milano) 6:353–357.Google Scholar
  67. 67.
    Livne E, von der Mark K, Silbermann M (1985) Morphologic and cytochemical changes in maturing and osteoarthritic articular cartilage in the temporomandibular joint of mice. Arthritis Rheum 28: 1027–1038.PubMedGoogle Scholar
  68. 68.
    Lo MY, Kim HT (2004) Chondrocyte apoptosis induced by collagen degradation: inhibition by caspase inhibitors and IGF-1. J Orthop Res 22: 140–144.PubMedGoogle Scholar
  69. 69.
    Lo MY, Kim HT (2004) Chondrocyte apoptosis induced by hydrogen peroxide requires caspase activation but not mitochondrial pore transition. J Orthop Res 22:1120–1125.PubMedGoogle Scholar
  70. 70.
    Loeser RF (2000) Chondrocyte integrin expression and function. Biorheology 37:109–116.PubMedGoogle Scholar
  71. 71.
    Lohmander S (1988) Proteoglycans of joint cartilage. Structure, function, turnover and role as markers of joint disease. Baillieres Clin Rheumatol 2:37–62.PubMedGoogle Scholar
  72. 72.
    Lotz M (1999) The role of nitric oxide in articular cartilage damage. Rheum Dis Clin North Am 25: 269–282.PubMedGoogle Scholar
  73. 73.
    Lum JJ, Bauer DE, Kong M, Harris MH, Li C, Lindsten T, and Thompson CB (2005) Growth factor regulation of autophagy and cell survival in the absence of apoptosis. Cell 120:237–248.PubMedGoogle Scholar
  74. 74.
    Lyons TJ, Stoddart RW, McClure SF, and McClure J (2005) The tidemark of the chondro-osseous junction of the normal human knee joint. J Mol Histol 36:207–215.PubMedGoogle Scholar
  75. 75.
    Mankin HJ (1968) The effect of aging on articular cartilage. Bull NY Acad Sci 44:545–552.Google Scholar
  76. 76.
    Manninen P, Riihimaki H, Heliovaara M, and Makela P (1996) Overweight, gender and knee osteoarthritis. Int J Obes Relat Metab Disord 20:595–597.PubMedGoogle Scholar
  77. 77.
    Mansfield K, Pucci B, Adams CS, and Shapiro IM (2003) Induction of apoptosis in skeletal tissues: phosphate-mediated chick chondrocyte apoptosis is calcium dependent. Calcif Tissue Int 73:161–172.PubMedGoogle Scholar
  78. 78.
    Mansfield K, Rajpurohit R, Shapiro IM (1999) Extracellular phosphate ions cause apoptosis of terminally differentiated epiphyseal chondrocytes. J Cell Physiol 179:276–286.PubMedGoogle Scholar
  79. 79.
    Mansfield K, Teixeira CC, Adams CS, and Shapiro IM (2001) Phosphate ions mediate chondrocyte apoptosis through a plasma membrane transporter mechanism. Bone 28:1–8.PubMedGoogle Scholar
  80. 80.
    Maroudas A, Bayliss MT, and Venn MF (1980) Further studies on the composition of human femoral head cartilage. Ann Rheum Dis 39:514–523.PubMedGoogle Scholar
  81. 81.
    Maroudas A, Venn M (1977) Chemical composition and swelling of normal and osteoarthritic femoral head cartilage II. Collagen. Ann Rheum Dis 36:399–406.Google Scholar
  82. 82.
    Matsuo M, Nishida K, Yoshida A, Murakami T, and Inoue H (2001) Expression of caspase-3 and -9 relevant to cartilage destruction and chondrocyte apoptosis in human osteoarthritic cartilage. Acta Med Okayama 55:333–340.PubMedGoogle Scholar
  83. 83.
    Meachim G, Collins DH (1962) Cell counts of normal and osteoarthritic articular cartilage in relation to the uptake of sulfate (35SO_4) in vitro. Ann Rheum Dis 21:45–50.PubMedGoogle Scholar
  84. 84.
    Meachim G, Ghadially FN, Collins DH (1965) Regressive changes in the superficial layer of human articular cartilage. Ann Rheum 24:23–30.Google Scholar
  85. 85.
    Meijer AJ, Codogno P (2004) Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol 36:2445–2462.PubMedGoogle Scholar
  86. 86.
    Meredith D, Bell P, McClure B, and Wilkins R (2002) Functional and molecular characterisation of lactic acid transport in bovine articular chondrocytes. Cell Physiol Biochem 12:227–234.PubMedGoogle Scholar
  87. 87.
    Milz S, Putz R (1994) Quantitative morphology of the subchondral plate of the tibial plateau. J Anat 185:103–110.PubMedGoogle Scholar
  88. 88.
    Mistry D, Oue Y, Chambers MG, Kayser MV, and Mason RM (2004) Chondrocyte death during murine osteoarthritis. Osteoarthritis Cartilage 12:131–141.PubMedGoogle Scholar
  89. 89.
    Mitrovic D, Quintero M, Stankovic A, and Ryckewaert A (1983) Cell density of adult human femoral condylar articular cartilage. Joints with normal and fibrillated surfaces. Lab Invest 49:309–316.Google Scholar
  90. 90.
    Morishima N, Nakanishi K, Takenouchi H, Shibata T, and Yasuhiko Y (2002) An endoplasmic reticulum stress-specific caspase cascade in apoptosis. Cytochrome c-independent activation of caspase-9 by caspase-12. J Biol Chem 277:34287–34294.PubMedGoogle Scholar
  91. 91.
    Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, Packer M, Schneider MD, and Levine B (2005) Bcl-2 Antiapoptotic proteins inhibit beclin 1-dependent autophagy. Cell 122:927–939.PubMedGoogle Scholar
  92. 92.
    Perlot RL, Shapiro IM, Mansfield K, and Adams CS (2002) Matrix regulation of skeletal cell apoptosis II: role of arg- gly-asp-containing peptides. J Bone Miner Res 17:66–76.PubMedGoogle Scholar
  93. 93.
    Pettersen I, Figenschau Y, Olsen E, Bakkelund W, Smedsrod B, and Sveinbjornsson B (2002) Tumor necrosis factor-related apoptosis-inducing ligand induces apoptosis in human articular chondrocytes in vitro. Biochem Biophys Res Commun 296:671–676.PubMedGoogle Scholar
  94. 94.
    Poole CA, Zhang ZJ, Ross JM (2001) The differential distribution of acetylated and detyrosinated alpha-tubulin in the microtubular cytoskeleton and primary cilia of hyaline cartilage chondrocytes. J Anat 199:393–405.PubMedGoogle Scholar
  95. 95.
    Pulai JI, Del CM, Jr, Loeser RF (2002) The alpha5beta1 integrin provides matrix survival signals for normal and osteoarthritic human articular chondrocytes in vitro. Arthritis Rheum46:1528–1535.PubMedGoogle Scholar
  96. 96.
    Quintero M, Mitrovic D, Stankovic A, de Seze S, Miravet L, and Ryckewaert A (1984) Aspects cellulaires du viellissement du cartilage articulaire I. Cartilage condylien a surface normale, preleve dans les genoux normaux. Rev Rhum 51:375–379.PubMedGoogle Scholar
  97. 97.
    Quintero M, Mitrovic D, Stankovic A, de Seze S, Miravet L, and Ryckewaert A (1984) Aspects cellulaires du viellissement du cartilage articulaire II. Cartilage condylien a surface fissuree preleve dans les genoux “normaux” et “arthrosiques.” Rev Rhum 51:445–449.PubMedGoogle Scholar
  98. 98.
    Roach HI, Aigner T, Kouri JB (2004) Chondroptosis: a variant of apoptotic cell death in chondrocytes?. Apoptosis 9:265–277.PubMedGoogle Scholar
  99. 99.
    Roach HI, Erenpreisa J (1996) The phenotypic switch from chondrocytes to bone-forming cells involves asymmetric cell division and apoptosis. Connect Tissue Res 35:85–91.PubMedGoogle Scholar
  100. 100.
    Roach HI, Yamada N, Cheung KS, Tilley S, Clarke NM, Oreffo RO, Kokubun S, and Bronner F (2005) Association between the abnormal expression of matrix-degrading enzymes by human osteoarthritic chondrocytes and demethylation of specific CpG sites in the promoter regions. Arthritis Rheum 52:3110–3124.PubMedGoogle Scholar
  101. 101.
    Sandell LJ, Aigner T (2001) Articular cartilage and changes in arthritis. An introduction: cell biology of osteoarthritis. Arthritis Res 3:107–113.PubMedGoogle Scholar
  102. 102.
    Sepulveda JL, Gkretsi V, Wu C (2005) Assembly and signaling of adhesion complexes. Curr Topics Dev Biol 68:183–225.Google Scholar
  103. 103.
    Sharif M, Whitehouse A, Sharman P, Perry M, and Adams M (2004) Increased apoptosis in human osteoarthritic cartilage corresponds to reduced cell density and expression of caspase-3. Arthritis Rheum 50:507–515.PubMedGoogle Scholar
  104. 104.
    Shintani T, Klionsky DJ (2004) Autophagy in health and disease: a double-edged sword. Science 306:990–995.PubMedGoogle Scholar
  105. 105.
    Smith RL (1999) Degradative enzymes in osteoarthritis. Front Biosci 4:D704–D712.PubMedGoogle Scholar
  106. 106.
    Sokoloff L (1993) Microcracks in the calcified layer of articular cartilage. Arch Pathol Lab Med 117:191–195.PubMedGoogle Scholar
  107. 107.
    Spitzer JJ, Poolman B (2005) Electrochemical structure of the crowded cytoplasm. Trends Biochem Sci 30:536–541.PubMedGoogle Scholar
  108. 108.
    Stanton H, Rogerson FM, East CJ, Golub SB, Lawlor KE, Meeker CT, Little CB, Last K, Farmer PJ, Campbell IK, Fourie AM, and Fosang AJ (2005) ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature 434:648–652.PubMedGoogle Scholar
  109. 109.
    Stock J, Da Re S (2000) Signal transduction: response regulators on and off. Curr Biol 10:R420–R424.PubMedGoogle Scholar
  110. 110.
    Stockwell RA (1967) The cell density of human articular and costal cartilage. J Anat 101:753–763.PubMedGoogle Scholar
  111. 111.
    Struglics A, Larsson S, Pratta MA, Kumar S, Lark MW, and Lohmander LS 2006 Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase- and matrix metalloproteinase-generated aggrecan fragments. Osteoarthritis Cartilage 14:101–113.PubMedGoogle Scholar
  112. 112.
    Terkeltaub R, Johnson K, Murphy A, and Ghosh S (2002) The mitochondrion in osteoarthritis. Mitochondrion 1:301–319.PubMedGoogle Scholar
  113. 113.
    Todd Allen R, Robertson CM, Harwood FL, Sasho T, Williams SK, Pomerleau AC, and Amiel D (2004) Characterization of mature vs aged rabbit articular cartilage: analysis of cell density, apoptosis-related gene expression and mechanisms controlling chondrocyte apoptosis. Osteoarthritis Cartilage/OARS Osteoarthritis Research Society 12: 917–923.Google Scholar
  114. 114.
    Urban JPG, Hall AC (1992) Physical modifiers of matrix metabolism. In: Kuettner KE, Schleyerbach R, Peyron JG, Hascall VC, eds. Articular Cartilage and Osteoarthritis. New York: Raven Press, pp. 393–406.Google Scholar
  115. 115.
    Vignon E, Arlot M, Patricot LM, and Vignon G (1976) The cell density of human femoral head cartilage. Clin Orthop 121:303–308.PubMedGoogle Scholar
  116. 116.
    Whiteman M, Armstrong JS, Cheung NS, Siau JL, Rose P, Schantz JT, Jones DP, and Halliwell B (2004) Peroxynitrite mediates calcium-dependent mitochondrial dysfunction and cell death via activation of calpains. FASEB J 18:1392–1397.Google Scholar
  117. 117.
    Yang L, Carlson SG, McBurney D, and Horton WE, Jr (2005) 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 280:31156–31165.PubMedGoogle Scholar
  118. 118.
    Yatsugi N, Tsukazaki T, Osaki M, Koji T, Yamashita S, and Shindo H (2000) Apoptosis of articular chondrocytes in rheumatoid arthritis and osteoarthritis: correlation of apoptosis with degree of cartilage destruction and expression of apoptosis-related proteins of p53 and c-myc. J Orthop Sci 5:150–156.PubMedGoogle Scholar
  119. 119.
    Zemmyo M, Meharra EJ, Kuhn K, Creighton-Achermann L, and Lotz M (2003) Accelerated, aging-dependent development of osteoarthritis in alpha1 integrin-deficient mice. Arthritis Rheum 48:2873–2880.PubMedGoogle Scholar
  120. 120.
    Zysset PK, Sonny M, Hayes WC (1994) Morphology-mechanical property relations in trabecular bone of the osteoarthritic proximal tibia. J Arthroplast 9:203–216.Google Scholar

Copyright information

© Springer-Verlag London Limited 2007

Authors and Affiliations

  • Irving M. Shapiro
  • Christopher S. Adams
  • Vickram Srinivas
  • Theresa A. Freeman

There are no affiliations available

Personalised recommendations