Oxidative phosphorylation in bone cells

The role of energy metabolism in bone cells is an active field of investigation. Bone cells are metabolically very active and require high levels of energy in the form of adenosine triphosphate (ATP) to support their function. ATP is generated in the cytosol via glycolysis coupled with lactic acid fermentation and in the mitochondria via oxidative phosphorylation (OXPHOS). OXPHOS is the final convergent metabolic pathway for all oxidative steps of dietary nutrients catabolism. The formation of ATP is driven by an electrochemical gradient that forms across the mitochondrial inner membrane through to the activity of the electron transport chain (ETC) complexes and requires the presence of oxygen as the final electron acceptor. The current literature supports a model in which glycolysis is the main source of energy in undifferentiated mesenchymal progenitors and terminally differentiated osteoblasts, whereas OXPHOS appears relevant in an intermediate stage of differentiation of those cells. Conversely, osteoclasts progressively increase OXPHOS during differentiation until they become multinucleated and mitochondrial-rich terminal differentiated cells. Despite the abundance of mitochondria, mature osteoclasts are considered ATP-depleted, and the availability of ATP is a critical factor that regulates the low survival capacity of these cells, which rapidly undergo death by apoptosis. In addition to ATP, bioenergetic metabolism generates reactive oxygen species (ROS) and intermediate metabolites that regulate a variety of cellular functions, including epigenetics changes of genomic DNA and histones. This review will briefly discuss the role of OXPHOS and the cross-talks OXPHOS-glycolysis in the differentiation process of bone cells.