[Regulation of bone mass by osteocyte network]

Immobilization osteoporosis is a big issue in modern societies with aging population. Mechanical stress is essential for maintaining bone mass ; however, the mechanism of the regulation of bone mass by the osteocyte network, which comprises a communication system through processes and canaliculi throughout bone, still remains to be clarified. Therefore, it is urgent to reveal the mechanism of bone mass regulation at loaded and unloaded conditions and the physiological functions of the osteocyte network on osteoblasts and osteoclasts using appropriate mouse models such as a mouse line with the disrupted osteocyte function. We identified a novel mechanical stress-responsible molecule, pyruvate dehydrogenase kinase 4 (Pdk4) , whose expression was upregulated in osteoblasts at the unloaded condition, using a mouse model with the disrupted osteocyte function. We found that Pdk4 regulates Rankl expression in osteoblasts through the signal from the osteocyte network and induces osteoclastogenesis and bone resorption at the unloaded condition. The analyses using appropriate mouse models are gradually revealing the physiological roles of the osteocyte network, which were difficult to examine for a long time because of the anatomic sites of osteocytes that are embedded in bone matrix.