Mechanical response microRNA-145a-5p alleviates osteoarthritis by inhibiting inflammation and promoting chondrogenesis

Background: Osteoarthritis is characterized by cartilage wear or absence and is usually initiated by inflammation and abnormal mechanical stimulation. MicroRNAs have been identified as the main regulators of osteoarthritis, but the influence of miR-145a-5p on osteoarthritis has not been elucidated. In this study, we focused on the role of miR-145a-5p in cartilage.

Methods: Destabilization of the medial meniscus surgery (DMM) and RNA fluorescence in situ hybridization (RNA FISH) were performed to detect the expression level of miR-145a-5p in osteoarthritis. Interleukin-1β was used to simulate the inflammatory environment in vitro. The Flexcell device was used for mechanical stimulation. Agomir-145a-5p was injected intra-articularly into the DMM-induced osteoarthritis mouse model. Histopathological examinations, and Molecular Biology techniques were used to investigate the underlying mechanisms.

Results: The expression of miR-145a-5p was decreased in osteoarthritis mice, whereas its expression increased with prolonged chondrogenesis. Then, studies in vitro also confirmed the pro-chondrogenesis and interleukin-1β inhibitory ability of miR-145a-5p. Additionally, miR-145a-5p can be regulated by cyclic stretch stress, with physiological mechanical stimulation promotes, but excessive mechanical stimulation suppresses its expression. In addition, miR-145a-5p rescues DMM-induced osteoarthritis progression, which was observed through the intra-articular injection of agomiR-145a-5p.

Conclusions: MiR-145a-5p, a mechanical responder, alleviates osteoarthritis progression through promoting chondrogenesis and alleviating inflammation response. And intra-articular injection of miR-145a-5p alleviates osteoarthritis progression. These findings suggest that miR-145a-5p is a promising target for the treatment of osteoarthritis.

Chondrogenesis; Interleukin-1β; Mechanical; Osteoarthritis; miR-145a-5p.