Skip to main content

Advertisement

SpringerLink
Log in

Events in Articular Chondrocytes with Aging

  • Epidemiology and Pathophysiology (Mone Zaidi and Jeffrey I. Mechanick, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

It is well accepted that aging is one of the most prominent risk factors for the initiation and progression of osteoarthritis. One of the most pronounced age-related changes in chondrocytes is the exhibition of a senescent phenotype, which is the result of several factors including the accumulation of reactive oxygen species and advanced glycation end products. Compared with a normal chondrocyte, senescent chondrocytes exhibit an impaired ability to respond to many mechanical and inflammatory insults to the articular cartilage. Furthermore, protein secretion is altered in aging chondrocytes, demonstrated by a decrease in anabolic activity and increased production of proinflammatory cytokines and matrix-degrading enzymes. Together, these events may make the articular cartilage matrix more susceptible to damage and lead to the onset of osteoarthritis. A better understanding of the mechanisms underlying age-related chondrocyte pathophysiology may be critical for the development of novel therapeutic interventions for progressive joint diseases.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Cheng HJ, Hootman JM, Murphy LB, Langmaid GA, Helmick CG. Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation—United States, 2007–2009. MMWR Morb Mortal Wkly Rep. 2010;59:1261–5.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. 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 

  4. Buckwalter JA, Roughley PJ, Rosenberg LC. Age-related changes in cartilage proteoglycans: quantitative electron microscopic studies. Microsc Res Tech. 1994;28:398–408.

    Article  PubMed  CAS  Google Scholar 

  5. Bolton MC, Dudhia J, Bayliss MT. Age-related changes in the synthesis of link protein and aggrecan in human articular cartilage: implications for aggregate stability. Biochem J. 1999;337(Pt 1):77–82.

    Article  PubMed  CAS  Google Scholar 

  6. Fortier LA, Barker JU, Strauss EJ et al. The Role of Growth Factors in Cartilage Repair. Clin Orthop Relat Res 2011.

  7. Loeser RF, Shanker G, Carlson CS, 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;43:2110–20.

    Article  PubMed  CAS  Google Scholar 

  8. 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;15:491–8.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  10. Blaney Davidson EN, Scharstuhl A, Vitters EL, et al. Reduced transforming growth factor-beta signaling in cartilage of old mice: role in impaired repair capacity. Arthritis Res Ther. 2005;7:R1338–47.

    Article  PubMed  CAS  Google Scholar 

  11. Scharstuhl A, van Beuningen HM, Vitters EL, et al. Loss of transforming growth factor counteraction on interleukin 1 mediated effects in cartilage of old mice. Ann Rheum Dis. 2002;61:1095–8.

    Article  PubMed  CAS  Google Scholar 

  12. van Beuningen HM, van der Kraan PM, Arntz OJ, et al. Transforming growth factor-beta 1 stimulates articular chondrocyte proteoglycan synthesis and induces osteophyte formation in the murine knee joint. Lab Invest. 1994;71:279–90.

    PubMed  Google Scholar 

  13. van der Kraan PM, Blaney Davidson EN, van den Berg WB. A role for age-related changes in TGFbeta signaling in aberrant chondrocyte differentiation and osteoarthritis. Arthritis Res Ther. 2010;12:201.

    Article  PubMed  Google Scholar 

  14. Verzijl N, DeGroot J, Thorpe SR, et al. Effect of collagen turnover on the accumulation of advanced glycation end products. J Biol Chem. 2000;275:39027–31.

    Article  PubMed  CAS  Google Scholar 

  15. • Uribarri J, Woodruff S, Goodman S, et al. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010;110:911–16 e12. This is a database of how various food preparation methods affect levels of AGE formation in food.

    Article  PubMed  Google Scholar 

  16. Ulrich P, Cerami A. Protein glycation, diabetes, and aging. Recent Prog Horm Res. 2001;56:1–21.

    Article  PubMed  CAS  Google Scholar 

  17. • Nah SS, Choi IY, Lee CK, et al. Effects of advanced glycation end products on the expression of COX-2, PGE2 and NO in human osteoarthritic chondrocytes. Rheumatology (Oxford). 2008;47:425–31. This is a study determining the proinflammatory mechanisms of AGEs on chondrocytes.

    Article  CAS  Google Scholar 

  18. Nah SS, Choi IY, Yoo B, et al. Advanced glycation end products increases matrix metalloproteinase-1, -3, and −13, and TNF-alpha in human osteoarthritic chondrocytes. FEBS Lett. 2007;581:1928–32.

    Article  PubMed  CAS  Google Scholar 

  19. Huang CY, Lai KY, Hung LF et al. Advanced glycation end products cause collagen II reduction by activating Janus kinase/signal transducer and activator of transcription 3 pathway in porcine chondrocytes. Rheumatology (Oxford) 2011.

  20. Verzijl N, DeGroot J, Ben ZC, et al. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: a possible mechanism through which age is a risk factor for osteoarthritis. Arthritis Rheum. 2002;46:114–23.

    Article  PubMed  CAS  Google Scholar 

  21. Chen AC, Temple MM, Ng DM, et al. Induction of advanced glycation end products and alterations of the tensile properties of articular cartilage. Arthritis Rheum. 2002;46:3212–7.

    Article  PubMed  CAS  Google Scholar 

  22. Bank RA, Bayliss MT, Lafeber FP, et al. 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.

    PubMed  CAS  Google Scholar 

  23. Guimaraes EL, Empsen C, Geerts A, et al. Advanced glycation end products induce production of reactive oxygen species via the activation of NADPH oxidase in murine hepatic stellate cells. J Hepatol. 2010;52:389–97.

    Article  PubMed  CAS  Google Scholar 

  24. Yang K, Wang XQ, He YS, et al. Advanced glycation end products induce chemokine/cytokine production via activation of p38 pathway and inhibit proliferation and migration of bone marrow mesenchymal stem cells. Cardiovasc Diabetol. 2010;9:66.

    Article  PubMed  Google Scholar 

  25. Whaley-Connell A, McCullough PA, Sowers JR. The role of oxidative stress in the metabolic syndrome. Rev Cardiovasc Med. 2011;12:21–9.

    PubMed  Google Scholar 

  26. Avery SV. Molecular targets of oxidative stress. Biochem J. 2011;434:201–10.

    Article  PubMed  CAS  Google Scholar 

  27. Roberts RA, Laskin DL, Smith CV, et al. Nitrative and oxidative stress in toxicology and disease. Toxicol Sci. 2009;112:4–16.

    Article  PubMed  CAS  Google Scholar 

  28. Studer R, Jaffurs D, Stefanovic-Racic M, et al. Nitric oxide in osteoarthritis. Osteoarthritis Cartilage. 1999;7:377–9.

    Article  PubMed  CAS  Google Scholar 

  29. Hiran TS, Moulton PJ, Hancock JT. Detection of superoxide and NADPH oxidase in porcine articular chondrocytes. Free Radic Biol Med. 1997;23:736–43.

    Article  PubMed  CAS  Google Scholar 

  30. 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  PubMed  CAS  Google Scholar 

  31. Jallali N, Ridha H, Thrasivoulou C, et al. Vulnerability to ROS-induced cell death in ageing articular cartilage: the role of antioxidant enzyme activity. Osteoarthritis Cartilage. 2005;13:614–22.

    Article  PubMed  CAS  Google Scholar 

  32. • Blanco FJ, Rego I, Ruiz-Romero C. The role of mitochondria in osteoarthritis. Nat Rev Rheumatol. 2011;7:161–9. This is a review on the role mitochondrial dysfunction plays in the pathogenesis of OA.

    Article  PubMed  CAS  Google Scholar 

  33. Davies CM, Guilak F, Weinberg JB, et al. Reactive nitrogen and oxygen species in interleukin-1-mediated DNA damage associated with osteoarthritis. Osteoarthritis Cartilage. 2008;16:624–30.

    Article  PubMed  CAS  Google Scholar 

  34. Yudoh K, Nguyen T, Nakamura H, 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:R380–91.

    Article  PubMed  CAS  Google Scholar 

  35. Nakagawa S, Arai Y, Mazda O, et al. N-acetylcysteine prevents nitric oxide-induced chondrocyte apoptosis and cartilage degeneration in an experimental model of osteoarthritis. J Orthop Res. 2010;28:156–63.

    PubMed  CAS  Google Scholar 

  36. Nelson KK, Melendez JA. Mitochondrial redox control of matrix metalloproteinases. Free Radic Biol Med. 2004;37:768–84.

    Article  PubMed  CAS  Google Scholar 

  37. Marie PJ, Kassem M. Extrinsic mechanisms involved in age-related defective bone formation. J Clin Endocrinol Metab. 2011;96:600–9.

    Article  PubMed  CAS  Google Scholar 

  38. Shirazi R, Shirazi-Adl A. Computational biomechanics of articular cartilage of human knee joint: effect of osteochondral defects. J Biomech. 2009;42:2458–65.

    Article  PubMed  CAS  Google Scholar 

  39. Stevens JE, Binder-Macleod S, Snyder-Mackler L. Characterization of the human quadriceps muscle in active elders. Arch Phys Med Rehabil. 2001;82:973–8.

    Article  PubMed  CAS  Google Scholar 

  40. Sun HB. Mechanical loading, cartilage degradation, and arthritis. Ann N Y Acad Sci. 2010;1211:37–50.

    Article  PubMed  CAS  Google Scholar 

  41. Chang BD, Broude EV, Fang J, et al. p21Waf1/Cip1/Sdi1-induced growth arrest is associated with depletion of mitosis-control proteins and leads to abnormal mitosis and endoreduplication in recovering cells. Oncogene. 2000;19:2165–70.

    Article  PubMed  CAS  Google Scholar 

  42. • Shimada H, Sakakima H, Tsuchimochi K, et al. Senescence of chondrocytes in aging articular cartilage: GADD45beta mediates p21 expression in association with C/EBPbeta in senescence-accelerated mice. Pathol Res Pract. 2011;207:225–31. This is an in vivo model of aging used to elucidate mechanisms of chondrocyte senescence.

    Article  PubMed  CAS  Google Scholar 

  43. Hoffman B, Liebermann DA. Gadd45 modulation of intrinsic and extrinsic stress responses in myeloid cells. J Cell Physiol. 2009;218:26–31.

    Article  PubMed  CAS  Google Scholar 

  44. Martos-Rodriguez A, Santos-Alvarez I, Campo-Ruiz V, et al. Expression of CCAAT/enhancer-binding protein-beta (C/EBPbeta) and CHOP in the murine growth plate. Two possible key modulators of chondrocyte differentiation. J Bone Joint Surg Br. 2003;85:1190–5.

    Article  PubMed  CAS  Google Scholar 

  45. Xin H, Liu D, Songyang Z. The telosome/shelterin complex and its functions. Genome Biol. 2008;9:232.

    Article  PubMed  Google Scholar 

  46. Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet. 2008;42:301–34.

    Article  PubMed  CAS  Google Scholar 

  47. Thacker J, Zdzienicka MZ. The XRCC genes: expanding roles in DNA double-strand break repair. DNA Repair (Amst). 2004;3:1081–90.

    Article  CAS  Google Scholar 

  48. Guarente L. Diverse and dynamic functions of the Sir silencing complex. Nat Genet. 1999;23:281–5.

    Article  PubMed  CAS  Google Scholar 

  49. • Brandl A, Hartmann A, Bechmann V, et al. Oxidative stress induces senescence in chondrocytes. J Orthop Res. 2011;29:1114–20. This paper shows molecular mechanisms mediating the effects of oxidative stress on chondrocyte senescence.

    Article  PubMed  CAS  Google Scholar 

  50. Park WY, Park JS, Cho KA, et al. Up-regulation of caveolin attenuates epidermal growth factor signaling in senescent cells. J Biol Chem. 2000;275:20847–52.

    Article  PubMed  CAS  Google Scholar 

  51. Dai SM, Shan ZZ, Nakamura H, 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;54:818–31.

    Article  PubMed  CAS  Google Scholar 

  52. Yudoh K, Shi Y, Karasawa R. Angiogenic growth factors inhibit chondrocyte ageing in osteoarthritis: potential involvement of catabolic stress-induced overexpression of caveolin-1 in cellular ageing. Int J Rheum Dis. 2009;12:90–9.

    Article  PubMed  Google Scholar 

  53. Aigner T, Hemmel M, Neureiter D, 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;44:1304–12.

    Article  PubMed  CAS  Google Scholar 

  54. Horton Jr WE, Feng L, Adams C. Chondrocyte apoptosis in development, aging and disease. Matrix Biol. 1998;17:107–15.

    Article  PubMed  CAS  Google Scholar 

  55. Loeser RF, Pacione CA, Chubinskaya S. The combination of insulin-like growth factor 1 and osteogenic protein 1 promotes increased survival of and matrix synthesis by normal and osteoarthritic human articular chondrocytes. Arthritis Rheum. 2003;48:2188–96.

    Article  PubMed  CAS  Google Scholar 

  56. Allende JE, Allende CC. Protein kinases. 4. Protein kinase CK2: an enzyme with multiple substrates and a puzzling regulation. FASEB J. 1995;9:313–23.

    PubMed  CAS  Google Scholar 

  57. Lee SW, Song YS, Lee SY, et al. Downregulation of protein kinase CK2 activity facilitates tumor necrosis factor-alpha-mediated chondrocyte death through apoptosis and autophagy. PLoS One. 2011;6:e19163.

    Article  PubMed  CAS  Google Scholar 

  58. Taniguchi N, Carames B, Ronfani L, et al. Aging-related loss of the chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritis. Proc Natl Acad Sci U S A. 2009;106:1181–6.

    Article  PubMed  CAS  Google Scholar 

  59. Zhou Z, Akinbiyi T, Xu L, et al. Tendon-derived stem/progenitor cell aging: defective self-renewal and altered fate. Aging Cell. 2010;9:911–5.

    Article  PubMed  CAS  Google Scholar 

  60. Leong DJ, Li YH, Gu XI, et al. Physiological loading of joints prevents cartilage degradation through CITED2. FASEB J. 2011;25:182–91.

    Article  PubMed  CAS  Google Scholar 

  61. Yokota H, Goldring MB, Sun HB. CITED2-mediated regulation of MMP-1 and MMP-13 in human chondrocytes under flow shear. J Biol Chem. 2003;278:47275–80.

    Article  PubMed  CAS  Google Scholar 

  62. Felson DT, Lawrence RC, Dieppe PA, et al. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med. 2000;133:635–46.

    PubMed  CAS  Google Scholar 

  63. Hinton R, Moody RL, Davis AW, et al. Osteoarthritis: diagnosis and therapeutic considerations. Am Fam Physician. 2002;65:841–8.

    PubMed  Google Scholar 

  64. Sinkov V, Cymet T. Osteoarthritis: understanding the pathophysiology, genetics, and treatments. J Natl Med Assoc. 2003;95:475–82.

    PubMed  Google Scholar 

  65. Peat G, Croft P, Hay E. Clinical assessment of the osteoarthritis patient. Best Pract Res Clin Rheumatol. 2001;15:527–44.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  67. Fukui N, Ikeda Y, Ohnuki T, et al. Regional differences in chondrocyte metabolism in osteoarthritis: a detailed analysis by laser capture microdissection. Arthritis Rheum. 2008;58:154–63.

    Article  PubMed  CAS  Google Scholar 

  68. Visco DM, Johnstone B, Hill MA, et al. Immunohistochemical analysis of 3-B-(−) and 7-D-4 epitope expression in canine osteoarthritis. Arthritis Rheum. 1993;36:1718–25.

    Article  PubMed  CAS  Google Scholar 

  69. •• Loeser RF. Age-related changes in the musculoskeletal system and the development of osteoarthritis. Clin Geriatr Med. 2010;26:371–86. This is a review on the effect of aging joint tissues on the development of OA.

    Article  PubMed  Google Scholar 

  70. Traustadottir T, Davies SS, Su Y, et al. Oxidative stress in older adults: effects of physical fitness. Age (Dordr) 2011.

  71. Boor P, Celec P, Behuliak M, et al. Regular moderate exercise reduces advanced glycation and ameliorates early diabetic nephropathy in obese Zucker rats. Metabolism. 2009;58:1669–77.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The author thanks the National Institutes of Health for funding this work (AR52743 and AR47628).

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Leni and Peter W. May Department of Orthopedics, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1188, New York, NY, 10029, USA

    Daniel J. Leong & Hui B. Sun

Authors
  1. Daniel J. Leong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hui B. Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hui B. Sun.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leong, D.J., Sun, H.B. Events in Articular Chondrocytes with Aging. Curr Osteoporos Rep 9, 196–201 (2011). https://doi.org/10.1007/s11914-011-0070-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11914-011-0070-3

Keywords

Search

Navigation