Abstract
Skeletogenesis, remodeling, and maintenance in adult tissues are regulated by sequential activation of genes coding for specific transcription factors. The conserved Homeobox genes (HOX, in humans) are involved in several skeletal pathologies. Osteoarthritis (OA) is characterized by homeostatic alterations of cartilage and bone synthesis, resulting in cartilage destruction and increased bone formation. We postulate that alterations in HOX expression in Mesenchymal Stem cells (MSCs) are likely one of the causes explaining the homeostatic alterations in OA and that this altered expression could be the result of epigenetic regulation. The expression of HOX genes in osteoarthritic-derived MSCs was screened using PCR arrays. Epigenetic regulation of HOX was analyzed measuring the degree of DNA methylation in their promoters. We demonstrate the downregulated expression of HOXA9 and HOXC8 in OA-MSCs. However, their expression does not correlate with promoter methylation status, suggesting that other epigenetic mechanisms could be implicated in the regulation of HOX expression. Studies on the role of these genes under active differentiation conditions need to be addressed for a better knowledge of the mechanisms regulating the expression of HOX, to allow a better understanding of OA pathology and to define possible biomarkers for therapeutic treatment.
Highlights
Osteoarthritis (OA) is characterized by synovial joint cartilage deterioration, inflammation, and osteophyte formation
We studied the expression of HOX genes in Mesenchymal Stem cells (MSCs) and their correlation with their promoter methylation status
Bone marrow samples were obtained from the femoral channel at the time of surgery for total hip replacement of six patients with osteoarthritis
Summary
Osteoarthritis (OA) is characterized by synovial joint cartilage deterioration, inflammation, and osteophyte formation. It is the most prevalent and disabling degenerative joint disease in the elderly [1]. The exact pathogenetic mechanisms of OA are unknown. Two features of endochondral ossification, chondrocyte hypertrophy and apoptosis, have been proposed as mechanisms of OA initiation [5]. And biochemically, cartilage and subchondral bone are closely related structures of the joint affected in OA. Their implication likely results from alterations of their molecular crosstalk, leading to the imbalance between new tissue formation and degradation, preventing proper self-repair [6,7]. The key role of inflammation in OA progression is well documented [8,9]
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