Molecul ar epidemiological study of the regulation of bone and joint destruction through intracellular ATP and ROS levels

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Osteoclasts have two conflicting tendencies : lower capacity to survive and higher capacity to execute energy-consuming activities like bone resorption. Here, we report that mature mitochondria-rich osteoclasts have lower intracellular ATP compared to their precursors. Severe ATP depletion caused by disrupting the gene of mitochondrial transcription factor A(Tfam) leads to increased bone-resorbing activity despite accelerated apoptosis. The release of ATP from intracellular stores negatively regulates bone-resorbing activity through an autocrine/paracrine feedback loop by altering cytoskeletal structures. Thus, our study provides evidence for a mechanism by reciprocal changes in intracellular and extracellular ATP, which regulate the negative correlation between osteoclast survival and bone resorption.