Energy metabolism: A newly emerging target of BMP signaling in bone homeostasis

Energy metabolism is the process of generating energy (i.e. ATP) from nutrients. This process is indispensable for cell homeostasis maintenance and responses to varying conditions. Cells require energy for growth and maintenance and have evolved to have multiple pathways to produce energy. Both genetic and functional studies have demonstrated that energy metabolism, such as glucose, fatty acid, and amino acid metabolism, plays important roles in the formation and function of bone cells including osteoblasts, osteocytes, and osteoclasts. Dysregulation of energy metabolism in bone cells consequently disturbs the balance between bone formation and bone resorption. Metabolic diseases have also been reported to affect bone homeostasis. Bone morphogenic protein (BMP) signaling plays critical roles in regulating the formation and function of bone cells, thus affecting bone development and homeostasis. Mutations of BMP signaling-related genes in mice have been reported to show abnormalities in energy metabolism in many tissues, including bone. In addition, BMP signaling correlates with critical signaling pathways such as mTOR, HIF, Wnt, and self-degradative process autophagy to coordinate energy metabolism and bone homeostasis. These findings will provide a newly emerging target of BMP signaling and potential therapeutic strategies and the improved management of bone diseases. This review summarizes the recent advances in our understanding of (1) energy metabolism in regulating the formation and function of bone cells, (2) function of BMP signaling in whole body energy metabolism, and (3) mechanistic interaction of BMP signaling with other signaling pathways and biological processes critical for energy metabolism and bone homeostasis.