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Cellular and epigenetic features of a young healthy and a young osteoarthritic cartilage compared with aged control and OA cartilage

By M.A. da Silva, N. Yamada, N.M. Clarke and H.I. Roach

Abstract

Osteoarthritis (OA) is generally a disease of the elderly population, but can occur in young patients in exceptional cases. This study compares the cellular and epigenetic features of primary old-age OA with those of secondary OA in a 23-year old patient with Developmental Dysplasia of the Hip. In addition, control cartilage from a 14-year old was compared with that from patients with a fracture of the neck of femur (#NOF) to establish to what extent the latter is a useful control for OA. Articular cartilage was obtained from discarded femoral heads after hip arthroplasty. MMP-3, MMP-9, MMP-13 and ADAMTS-4 were immuno-localized and the methylation status of specific promoter CpG sites was determined. Both primary and secondary OA were characterized by loss of aggrecan, formation of clones, abnormal expression of the proteases that correlated with epigenetic DNA de-methylation The latter indicated that the abnormal expression of the cartilage-degrading proteases was not due to a short-term up-regulation, but a heritable, permanent alteration in gene expression. Comparing cell densities in young and old control cartilage estimated an age-related cell loss of ~1% per year. In aged #NOF cartilage, some superficial-zone chondrocytes expressed the proteases, but the majority of cells were immuno-negative and their promoters were hypermethylated. The cellular and epigenetic features of the intermediate and deep zones of #NOF cartilage are thus similar to those of young healthy cartilage, justifying the use of #NOF cartilage as control cartilage for OA, providing the superficial zone is removed

Topics: RZ
Year: 2008
OAI identifier: oai:eprints.soton.ac.uk:72831
Provided by: e-Prints Soton

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Citations

  1. (2006). Adult hip dysplasia and osteoarthritis. Studies in radiology and clinical epidemiology. Acta Orthop Suppl 77:1–37. doi
  2. (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. doi
  3. (2003). Changes in the antiangiogenic properties of articular cartilage in osteoarthritis. doi
  4. (2004). Chondroptosis: a variant of apoptotic cell death in chondrocytes? Apoptosis 9:265–277. doi
  5. (2007). DNA methylation in osteoarthritic chondrocytes: a new molecular target. Osteoarthritis Cartilage 15:128–137. doi
  6. (1995). Expression of type-X collagen in osteoarthritis. doi
  7. (2002). Identification of the metalloproteinase stromelysin in the physis. doi
  8. (2004). Joint replacement for sequelae of childhood hip disorders. doi
  9. (2007). Mechanisms of disease: role of chondrocytes in the pathogenesis of osteoarthritis-structure, chaos and senescence. Nat Clin Pract Rheumatol 3:391–399. doi
  10. (2007). Mechanisms of epigenetic inheritance. doi
  11. (2003). Osteoarthritis and osteoporosis: clinical and research evidence of inverse relationship. Aging Clin Exp Res 15:426–439. doi
  12. (2006). Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage 14:13–29. doi
  13. (2006). Osteoarthritis: Pathobiology-targets and ways for therapeutic intervention. Adv Drug Deliv Rev 58:128–149. doi
  14. (2000). Physiological cell death of chondrocytes in vivo is not confined to apoptosis: doi
  15. (2005). 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 7:R380–R391.
  16. (1994). Regional and temporal changes in the synthesis of matrix metalloproteinases and TIMP-1 during development of the rabbit mandibular condyle.
  17. (2002). The natural history of developmental dysplasia of the hip after early supervised treatment in the Pavlik harness. A. prospective, longitudinal follow-up. doi
  18. (2007). The Pathogenesis of Osteoarthritis. In: doi
  19. (2003). The role of chondrocyte senescence in the pathogenesis of osteoarthritis and in limiting cartilage repair.
  20. (1993). Type X collagenexpression in osteoarthritic andrheumatoidarticular cartilage.
  21. (2006). Update on the biology of the chondrocyte and new approaches to treating cartilage diseases. Best Pract Res Clin Rheumatol 20:1003–1025. doi

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