期刊
JOURNAL OF ORTHOPAEDIC RESEARCH
卷 27, 期 5, 页码 593-601出版社
WILEY
DOI: 10.1002/jor.20799
关键词
osteoarthritis; epigenetics; developmental dysplasia of the hip (DDH); DNA methylation; articular chondrocytes
类别
资金
- Wessex Medical Trust [Nr. K06, L03]
- Great Hip and Knee Walkers of Southampton
- Sendai (Japan)
- CNPq (Ministry of Science and Technology of Brazil)
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 similar to 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. (C) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:593-601, 2009
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