Study on the role of Peroxisome Proliferator-Activated Receptors (PPARs) in the immune regulatory activities during mesenchymal stem cell differentiation

Mesenchymal stem cells (MSCs) are self-renewable multipotent progenitor cells that can differentiate into a variety of cell types including adipocytes, osteocytes and chondrocytes. Recent studies have demonstrated that MSCs could exert an immunosuppressive activity. However, many obesity-related metabolic diseases such as type II diabetes are attributed to adipocyte-induced inflammation. Macrophages recruited by adipose tissue-derived hormones or chemokines, play the key roles in the chronic inflammation. We hypothesized that some mediators might be changed during the MSCs adipogenesis. Especially, the role of PPAR-γ in inflammation and anti-inflammation are still unclear. Hence, this study was performed to examine the gene and cytokine profiles of MSCs in different differential process. Alone with MSCs adipogenesis, more inflammatory cytokines, including IL-6, TNF-α, and mcp1 were secreted and expressed. But the expression of MSCs surface markers and immune-modulatory function were decreased. Also, the expression of IL-1Ra was negatively correlated with adipogeneic process of MSCs. Furthermore, peroxisome proliferator-activated receptors (PPARs) can promote adipogenesis by inhibiting IL-1Ra expression. So far, we discovered that adding PPAR-γ agonist could enhance adiponectin and inflammatory genes expression. On the other hand, adding PPAR-γ antagonist resulted in the opposite effects. Further, the cells of PPAR-γ agonist and antagonist group inhibited phenotypic change or adipogenic progressing. Also, agonist and antagonist decreased MSCs immunosuppressive function during adipogenic process. We would like to find out if there is any factor that can directly influence MSCs adipogenesis and their immune-suppressive function.