Exosomes Extracted from Human Umbilical Cord MSCs Contribute to Osteoarthritic Cartilage and Chondrocytes Repair Through Enhancing Autophagy While Suppressing the Wnt/β-Catenin Pathway.

Abstract

Background: Osteoarthritis (OA), a widespread chronic joint disorder mainly affecting the elderly, currently lacks a definitive cure. This study investigated the efficacy of exosomes (Exos) extracted from human umbilical cord MSCs (hucMSCs) in the treatment of OA, and preliminarily explored the mechanisms.

Methods: A rat osteoarthritis model was constructed by surgical induction. The cartilage morphology was observed after pathological staining; expression of cartilage matrix protein, autophagy-related protein and β-catenin were detected by immunohistochemistry; and inflammatory factors in serum were tested by ELISA. In cellular experiments, human primary chondrocytes were induced with IL-1β to build the OA microenvironment. The levels of relevant proteins in each group were analyzed.

Results: Comparing to the OA model, the Exos treatment showed positive effects in reducing OARSI score and Mankin score, decreasing joint space stenosis, promoting matrix synthesis, increasing autophagy, and decreasing β-catenin. The results of the cellular experiments were consistent with those from the animal experiments. However, the Wnt/β-catenin pathway was greatly activated, the levels of matrix proteins and autophagy were distinctly reduced in the Exos + LiCl group comparing to the exosome-treated group.

Conclusion: hucMSCs-Exos effectively attenuated the pathological damage of OA cartilage and chondrocytes, promoted the synthesis of cartilage matrix, reduced inflammation, suppressed the Wnt/β-catenin pathway, and enhanced autophagy which promoted the repair of OA cartilage.