The Role of mTOR in Osteoclasts

Evolutionary conserved kinase mechanistic target of rapamycin (mTOR) is the signaling hub for cellular responses to nutrients, cytokines, growth hormones, and environmental stresses in all eukaryotic cells. Increased mTOR activity has been demonstrated in numerous diseases, such as cancer and autoimmune diseases. Due to its prominent role, mTOR inhibitors are being used and tested to treat a wide variety of conditions. Recent evidence suggests that regulation of mTOR activity and function is not universal and varies between the cells. Here we summarize the latest research on the role and regulation of mTOR in osteoclasts, the unique multinucleated bone-resorbing cells, focusing on the role of mTOR as part of the mTORC1 complex. Collectively, the results suggest that mTORC1 activity plays a double role in osteoclastogenesis: at the earlier stage, it is necessary for proliferation of the precursors, and, at the later stage, it is indispensable for cytoskeletal reorganization involved in the process of bone resorption. We also present evidence that in osteoclasts, mTOR protein levels and activity are regulated differently compared to other primary cells and cell lines. Due to this prominent role of mTOR in osteoclast formation and function, mTOR inhibitors could be used to treat numerous diseases that involve overactive osteoclasts, such as osteoporosis, inflammatory arthritis, Paget’s disease, and cancer-related osteolysis.