Hsa_circ_0000077-Overexpressing Synovial Mesenchymal Stem Cell: A New Tool for Cartilage Regeneration

Background & Aim Osteoarthritis (OA) is a common disabling disease, which at present there is nearly no effective medical treatment. Due to the poor self-healing ability of articular cartilage, even small cartilage defects (if untreated) would ultimately lead to OA. Stem cells/chondrocytes transplantation has increasingly been considered as potential approaches in cartilage tissue engineering. Chondrocytes transplantation has a limited source, and meanwhile ordinary stem cells transplantation has a limited ability to differentiate into cartilage. In preliminary study, we found that decreased expression of hsa_circ_0000077 (circ77) was associated with the development of OA, and circ77 can prevent the chondrocyte degeneration. Therefore, in this study, a promising seed cell, circ77-overexpressing synovial mesenchymal stem cell (77-SMSC), has the ability to be a new tool for cartilage regeneration. Methods, Results & Conclusion In clinical samples, gene expression levels of circ77 were measured by qPCR. The expression level of circ77 in healthy cartilage was significantly higher than in OA cartilage. CCK-8, qPCR and western blotting (WB) were used to investigate the biological functions of circ77 on the proliferation and chondrogenic differentiation. CCK-8 assay confirmed that overexpression of circ77 enhanced the proliferation of synovial mesenchymal stem cell (SMSC). Western blotting and qPCR assays confirmed that overexpression of circ77 enhanced cartilage related proteins including SOX9, Type II collagen and aggrecan. Chondrogenic differentiation induction assays with Alcian Blue staining were used to assess the ability of chondrogenic differentiation. And the assays showed that 77-SMSCs had enhanced chondrogenic differentiation ability than ordinary SMSCs. Our results have revealed that 77-SMSC had advanced chondrogenic differentiation capacity, and would be not only a new type of seed cells, but also a potential powerful cell therapy approach in cartilage tissue engineering.