Joint Distraction Combined with Mesenchymal Stem Cell Intra-articular Injection Attenuates Osteoarthritis

Abstract Background: Conservative treatments of osteoarthritis (OA) are limited to symptom relief and novel methods to attenuate OA progression are lacking. Objective: In this study, we investigated the effectiveness of knee joint distraction (KJD) combined with mesenchymal stem cells (MSCs) intra-articular injection (KJD+MSCs) in OA rat model. Methods: OA rat model was established by anterior cruciate ligament transection plus medial meniscus resection in right knee in SD rat. The KJD+MSCs treatment started 3 weeks after the OA surgery. There were two other groups as knee joint distraction only (KJD) and no treat (OA). Three weeks after the treatment, distraction external fixators were removed and rats were kept for further 3 weeks. The rats were then terminated, samples were subject to micro-CT and histology examinations to evaluate the changes of the articular cartilage tissues, subchondral bone and the secondary inflammation. Results: Safranin-O/fast green staining showed that articular cartilage injury was most obvious in the OA group than that in the KJD group and the least in the KJD+MSCs group. Immunohistochemistry examinations showed that the KJD+MSCs group had the lowest percentage of MMP13 or ColX positive chondrocytes comparing to other groups. Micro-CT data indicated that the abnormal change in the subchondral region of the tibia in the KJD+MSCs group was significantly less than that in the KJD group or OA group. Finally, immunohistochemistry result showed that the knee joint in the KJD+MSCs group had the least number of CD68-positive cells among all the groups. Conclusions: Joint distraction combined with mesenchymal stem cells injection alleviated cartilage degradation, reduced irregular ossification of subchondral bone and secondary inflammation, suggesting it could be a new method to halt the OA progression.