Differentiation of Human Mesenchymal Stem Cells: The Potential Mechanism for Estrogen-Induced Preferential Osteoblast Versus Adipocyte Differentiation

Introduction: Bone marrow-derived mesenchymal stem cells (MSCs) are capable of differentiating into osteoblasts and adipocytes. This critical balance between osteoblast and adipocyte differentiation plays a significant role in maintaining normal bone homeostasis. In osteoporosis, a metabolic bone disease seen mainly in postmenopausal women because of estrogen deficiency, the concomitant occurrence of increased bone marrow adipocyte production with diminished production of osteoblasts, points to the potential role of estrogen in shifting the balance of MSC differentiation. Methods: We established an in vitro differentiation model of isolated human MSCs (hMSCs) and examined the role of distinct estrogen signaling pathways in regulating the differentiation of hMSCs. Results: Estrogen promoted the differentiation of hMSCs to osteoblasts in contrast to adipocytes, the former of which was mediated through the PI3K/SSH1L but not the mitogen-activated protein kinase pathway. Conclusion: This study provides a novel mechanistic understanding of estrogen-related osteoporosis and identifies potential targets for antiosteoporosis therapies.