Peroxisome proliferator-activated receptor-γ and its related pathway in bone marrow mesenchymal stem cell differentiation co-cultured with mechanically stretched ligament fibroblasts

Abstract

The occurrence of pelvic floor dysfunctional disease (PFD) is closely related with elasticity, toughness, and functional changes of the connective tissue of the pelvic support tissue. Bone marrow mesenchymal stem cells (BMSCs) have been confirmed to have the capacity to differentiate into a variety of cell types such as osteoblasts, chondroblasts, adipocytes and fibroblasts. Therefore, BMSCs have the potential to improve the clinical outcomes for PFD. Peroxisome proliferator-activated receptor-γ (PPAR-γ), a ligand activated transcription factor, has acquired a great deal of attention as it is involved in the fibrosis and cell differentiation. However, how it is regulated during the process of the differentiation of BMSCs into fibroblasts remains to be defined. The present study investigated the underlying mechanisms of PPAR-γ effect of mechanical stretch on the differentiation of BMSCs induced by pelvic ligament fibroblasts. PPAR-γ expression was decreased during the differentiation of BMSCs into fibroblasts by co-cultured stretched fibroblasts. Addition of transforming growth factor-β1 (TGF-β1) reduced PPAR-γ expression and promoted the differentiation of BMSCs. With the employment of endogenous ligand, activation of PPAR-γ suppressed the BMSC differentiation. Similar effects were also observed with overexpression of PPAR-γ gene. In addition, decrease of PPAR-γ by the use of shRNA targeting rat PPAR-γ significantly contributed to BMSC differentiation to fibroblasts. These results indicate that PPAR-γ negatively regulates the differentiation of BMSCs into fibroblasts.