Research ArticleOsteoarthritis

Stress-activated miR-204 governs senescent phenotypes of chondrocytes to promote osteoarthritis development

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Science Translational Medicine  03 Apr 2019:
Vol. 11, Issue 486, eaar6659
DOI: 10.1126/scitranslmed.aar6659

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Stress, senescence, and joint health

Oxidative stress increases with aging and contributes to osteoarthritis (OA), a form of degenerative joint disease affecting cartilage and bone. Kang et al. investigated the role of cartilage cell (chondrocyte) senescence in OA. Oxidative stress induced DNA damage and senescence in chondrocytes. miR-204 was up-regulated in senescent chondrocytes and in aged and osteoarthritic human cartilage. Mice treated with miR-204 exhibited accelerated cartilage degeneration and maladaptive changes in extracellular matrix content, particularly a reduction in proteoglycan synthesis. Treatment with anti–miR-204 rescued cartilage catabolism in a posttraumatic OA mouse model and ex vivo human OA cartilage explants. This study identifies a pathway important for cartilage matrix homeostasis.