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

Marco A. Da Silva, Norikazu Yamada, Nicholas M.P. Clarke, Helmtrud I. Roach

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    56 Citations (Scopus)

    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 immunolocalized 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, and abnormal expression of the proteases that correlated with epigenetic DNA demethylation. 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 immunonegative 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.

    Original languageEnglish
    Pages (from-to)593-601
    Number of pages9
    JournalJournal of Orthopaedic Research
    Volume27
    Issue number5
    DOIs
    Publication statusPublished - 2009 May

    Keywords

    • Articular chondrocytes
    • DNA methylation
    • Developmental dysplasia of the hip (DDH)
    • Epigenetics
    • Osteoarthritis

    ASJC Scopus subject areas

    • Orthopedics and Sports Medicine

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