Low FasL levels promote proliferation of human bone marrow-derived mesenchymal stem cells, higher levels inhibit their differentiation into adipocytes

摘要: Mesenchymal stem cells (MSCs) are multipotent progenitor that can differentiate into several cell types. Bone marrow (BM)–MSCs mainly osteoblasts or adipocytes. MSC interactions with their microenvironment directly affect self-renewal/differentiation program. Here, we show for the first time Fas ligand (FasL), a well-explored proapoptotic cytokine, promote proliferation of BM-derived MSCs in vitro and inhibits differentiation BM–MSCs treated low FasL dose (0.5 ng/ml) proliferated more rapidly than untreated without undergoing spontaneous apoptosis, whereas higher doses (25 ng/ml) induced significant though not massive BM–MSC death, surviving maintaining phenotype. At molecular level, 0.5 ng/ml ERK1/2 phosphorylation survivin upregulation, 25 ng/ml caspase activation. Importantly, reversibly prevented adipocytes by modulating peroxisome proliferator-activated receptor gamma (PPARγ) FABP4/aP2 expression adipogenic medium. All such effects were inhibited anti-Fas neutralizing antibody. The data regarding adipogenesis confirmed using Faslpr mutant mice, where PPARγ mRNA protein levels documented whole tibia. These FasL/Fas system have role biology via regulation both adipogenesis, may clinical relevance because circulating Fas/FasL decline age age-related conditions, including osteoporosis, characterized adipocyte accumulation BM.