Human Umbilical Cord Mesenchymal Stem Cells Inhibit the Progression of Osteoarthritis by Suppressing NLRP3-Mediated Synovial Inflammation in the Early Stages of the Disease.

Abstract

Osteoarthritis (OA) is the leading joint disease that causes joint pain and disability. Despite increasing progress regarding the therapeutic potential of human umbilical cord mesenchymal stem cells (UC-MSCs) for OA, effective strategies for the treatment of OA using UC-MSCs have not yet been developed in clinical practice. Our present study has proven that the early stage in OA rats is the main development stage of nod-like receptor heat protein domain protein 3 (NLRP3)-mediated synovial inflammation. The middle stage in OA rats is the main development stage of chondrocyte apoptosis. The late stage in OA rats is the main development stage of synovial fibrosis. The treatment of UC-MSCs in the early and middle stages of OA significantly reduced cartilage damage in rats, and improved the pathological structure of the knee joint. In comparison, UC-MSCs effectively reduced chondrocyte apoptosis in the early and middle stages of OA rats, but they only effectively reduced NLRP3-mediated synovial inflammation in the early stages of OA rats. Experiments in vitro showed that UC-MSCs could inhibit NLRP3-mediated pyroptosis of rat primary synovial cells (Rat-scs). In conclusion, our findings suggest that UC-MSCs exert therapeutic effects on OA, at least in part, through inhibiting NLRP3-mediated synovial inflammation in the early stage of OA.