Abstract
Osteoarthritis is a common cause of functional deterioration in older adults and is an immense burden on the aging population. Altered chondrogenesis is the most important pathophysiological process involved in the development of osteoarthritis. However, the molecular mechanism underlying the regulation of chondrogenesis in patients with osteoarthritis requires further elucidation, particularly with respect to the role of microRNAs. MiR-21 expression in cartilage specimens was examined in 10 patients with knee osteoarthritis and 10 traumatic amputees. The effect of miR-21 on chondrogenesis was also investigated in a chondrocyte cell line. The effect of miR-21 on the expression of growth differentiation factor 5 (GDF-5) was further assessed by luciferase reporter assay and western blot. We found that endogenous miR-21 is upregulated in osteoarthritis patients, and overexpression of miR-21 could attenuate the process of chondrogenesis. Furthermore, we identified GDF-5 as the direct target of miR-21 during the regulation of chondrogenesis. Our data suggest that miR-21 has an important role in the pathogenesis of osteoarthritis and is a potential therapeutic target.
Highlights
Osteoarthritis is a widely prevalent disease characterized by the progressive destruction of cartilage and is responsible for a majority of the health and economic burden in the elderly population worldwide.[1]
Chondrogenesis occurs as a result of chondrocyte cell condensation, proliferation and differentiation, the dysregulation of which would eventually lead to osteoarthritis.[3]
MiR-21 inhibits chondrocyte proliferation Because miR-21 was markedly increased in osteoarthritis, it might function as a promoter of osteoarthritis
Summary
Osteoarthritis is a widely prevalent disease characterized by the progressive destruction of cartilage and is responsible for a majority of the health and economic burden in the elderly population worldwide.[1]. MiRNAs are crucial for all cellular processes and have an important role in the process of chondrogenesis and cartilage remodeling.[2,5,6] As a result, aberrant miRNA expression profiles have been demonstrated to be associated with osteoarthritis development.[7,8,9,10] Previous studies have demonstrated a signature of 16 miRNAs that distinguishes normal from osteoarthritic cartilage tissue, with 9 miRNAs significantly upregulated and 7 miRNAs downregulated in osteoarthritis tissue compared with normal controls.[8]
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