Platelets Ameliorate Osteoarthritis Via ADP Stimulated Chondrocyte Proliferation

Osteoarthritis (OA) is the most common orthopedic disorder and reason of morbidity among elderly population worldwide. Currently, there is no effective treatment for OA. Recent studies indicate that platelet rich plasma (PRP) or platelet releasate is beneficial for the treatment of OA, the mechanism is however, poorly understood. The present study therefore aims to clarify the mechanism of platelet treatment on OA. Our data demonstrate that platelet co-culture indeed favored cartilage repair, a process involving an increased proliferation capability and decreased catabolic activities of chondrocytes. Furthermore, we obtained chondrocyte gene profile altered by platelet co-culture and demonstrated a significantly increased bone morphogenetic protein 7 (BMP7) production and secretion. The autocrine effect of BMP7 was responsible for the increased proliferation of chondrocytes, via ERK/CDK1/cyclin B1 signaling pathway. Platelet-derived ADP was identified as the major mediator to promote the production of BMP7 and proliferation of chondrocytes, through ADP receptor P2Y1. Finally, direct injection of a hydrolysis-resistant analog of ADP, a,P-Methyleneadenosine 5’-diphosphate (α,β-MeADP), into the OA joints also enhanced cartilage repair. The current study suggested that platelets promote chondrocyte BMP7 production and proliferation by secreted ADP and chondrocyte P2Y1 receptor. This finding may provide a key explanation to the therapeutic effect of platelet in OA and help shaping a better strategy to improve the OA therapy.