Bone marrow mesenchymal stem cells: fat on and blast off by FGF21.

Bone marrow mesenchymal stem cells (BMMSCs) are multipotent marrow stromal cells with the ability to differentiate into a variety of cell types required for tissue regeneration including osteoblasts and chondrocytes. Thus, they hold tremendous potential as powerful therapeutic strategies for the prevention and treatment of degenerative disorders including osteoporosis and osteoarthritis. The differentiation of BMMSCs into competing lineages such as osteoblasts and marrow adipocytes is regulated by various environmental cues and intrinsic signaling pathways. Here I highlight recent advances in the understanding of BMMSC function and regulation, including the interaction between BMMSCs with the hematopoietic/immune system, and the identification of novel modulators of BMMSC differentiation such as the metabolic hormone fibroblast growth factor 21 (FGF21). These new findings will further elucidate the dynamic regulation of BMMSCs in the pathophysiological control of skeletal homeostasis, and facilitate the clinical applications of BMMSCs in regenerative medicine.