Expression patterns of transcription factor PPAR gamma and C/EBP family members during in vitro adipogenesis of human bone marrow mesenchymal stem cells

摘要

In the past decades increasing lines of evidence have demonstrated that adipose tissue, as an endocrine organ plays a central role in metabolic homeostasis and its related maladies. CCAAT/enhancer-binding protein (C/EBP) family members and the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR) were known to be the vital transcription factors in the regulation of adipogenesis. However, the exact mechanism for increased marrow fat in patients with bone metabolic diseases, such as osteoporosis, is still poorly understood. Herein, we studied the expression pattern of PPAR and C/EBPs in human bone marrow mesenchymal stem cell (hBMSC) adipogenesis and evaluated the effects of individual components of an adipogenic cocktail on the differentiation and transcription factor expression. We furthermore examined whether the ERK signaling pathway was involved in mediating these effects. These findings showed that C/EBP and C/EBP were detected in undifferentiated hBMSC and maintained during the whole process of adipogenesis, and could initiate the expression of PPAR1 under the treatment of dexamethasone and IBMX. Subsequently, the activation of PPAR1 by indomethacin, its exogenous ligand, activated C/EBP, which, together with IBMX, up-regulated PPAR2 expression and therefore the fullest adipogenesis. Insulin and its downstream signal pathway extracellular signal-regulated kinases (ERK), however, were found not necessary for hBMSC adipogenesis. Our results revealed some unique characteristics of human adipocyte formation, which may help to understand the molecular mechanisms of bone marrow adipogenesis and give insights into the treatment of osteoporosis.