SEMA6D, Negatively Regulated by miR-7, Contributes to C28/I2 chondrocyte's Catabolic and Anabolic Activities via p38 Signaling Pathway

MiR-7 has been recognized as an osteoarthritis (OA-)-promoting factor, but the specific downstream pathway of miR-7 still remains unknown. Further investigation of the molecular regulatory mechanism of miR-7 might help develop a novel therapeutic method for OA. In this study, we revealed that Semaphorin 6D (SEMA6D) was a direct target gene of miR-7 and presented a negative regulatory relation with SEMA6D in vitro and in vivo. SEMA6D could improve OA in rat OA models, as indicated by H&E and Safranin O-Fast green staining, and also μCT analysis. Further evaluation of SEMA6D suggested that SEMA6D promotes the anabolism and reduces the catabolism of C28/I2 chondrocytes via inhibiting the activation of the p38 pathway. The present research illustrated that SEMA6D is a negatively regulatory factor of miR-7 and a pivotal mediator of catabolism and anabolism in C28/I2 chondrocytes. SEMA6D exerts its function via inhibiting the activation of the p38 pathway.