Conclusions
Our results collectively indicated that FSH plays an essential role in the pathogenesis of OA and acts as a crucial mediator.
Methods
Chondrocyte-like ATDC5 cells were treated with recombinant FSH protein. Then the cell viability was measured using cell counting kit-8 assay. Expressions of crucial factors involved in the extracellular matrix (ECM) metabolic and PKA-CREB-SOX9 pathway were analyzed by western blot, RT-qPCR, and immunofluorescence staining. Intracellular cAMP levels were assessed by ELISA assay. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM) surgery. Adeno-associated virus expressing shRNA against FSHR (AAV-shFSHR) was intra-articular (IA) injected into the OA model animals to specifically knock down FHSR in cartilage. Histological staining and OARSI scores were used to assess the efficacy of AAV-shFSHR injections.
Results
We found that FSH down-regulated the expression of ECM-related proteins in chondrocyte-like ATDC5 cells. The underlying mechanism is probably associated with regulating PKA/CREB/SOX9 pathway. Besides, blocking FSH signaling via shRNA-mediated downregulation of FSHR in joint tissues effectively delayed the development of posttraumatic OA in mice. Conclusions: Our results collectively indicated that FSH plays an essential role in the pathogenesis of OA and acts as a crucial mediator.