miR-26a deficiency is associated with bone loss and reduced muscle strength but does not affect severity of cartilage damage in osteoarthritis

Osteoarthritis (OA) is the most common age-related joint disease. However, the role of many microRNAs (miRNA) in skeletal development and OA pathogenesis has not been sufficiently elucidated using genetically modified mice with gain- and loss-of-function models. We generated Cartilage-specific miR-26a overexpressing (Col2a1-Cre;miR-26a Tgfl/fl: Cart-miR-26a Tg) mice and global miR-26a knockout (miR-26a KO) mice. The purpose of the present study was to determine the role of miR-26a in OA pathogenesis using aging and surgically induced models. Skeletal development of Cart-miR-26a Tg and miR-26a KO mice was grossly normal. Knee joints were evaluated by histological grading systems. In surgically-induced OA and aging models (12 and 18 months of age), Cart-miR-26a Tg mice and miR-26a KO mice exhibited OA-like changes such as proteoglycan loss and cartilage fibrillation with no significant differences in OARSI score (damage of articular cartilage) compared with control mice. However, miR-26a KO mice reduced muscle strength and bone mineral density at 12 months of age. These findings indicated that miR-26a modulates bone loss and muscle strength but has no essential role in aging-related or post-traumatic OA.