These results show that sensory nerve innervation contributes to the maintenance of trabecular bone mass and its mechanical properties by inhibiting bone resorption. Thus, there is a strong resemblance between sensory denervation and sympathetic activation in bone metabolism, suggesting that a sensory activity functionally interacts with the sympathetic activity in osteoclastic formation. Fig. 5 schematically represents a working hypothesis for the possible

interaction of sympathetic and sensory neurons. An in vitro co-culture experiment demonstrated AZD5363 that the responses to osteoblastic and osteoclastic cells produced by neural stimulation were inhibited by AR antagonists, suggesting that synaptic transmission occurs from nerve terminals to these cells. Specifically, the peripheral nerve

may be functionally and directly connected to the osteoblastic and osteoclastic cells for regulating bone metabolism in vivo. If osteoblastic activation is judged by cAMP, instead of the Ca2+ used in our study, it would be possible to analyze the molecular mechanism behind the communication mediated by NA acting through β-ARs. There is currently Dabrafenib great interest in comparing the cellular interaction with other cellular interactions, and in elucidating the physiological regulation of NA secretion in neuro-osteogenic synapses. Thus, the in vitro co-culture model is useful for studying the molecular mechanism responsible for the neuro-osteogenic cross-talk. In SHR with hyperactivity of the sympathetic nervous system, bone mass and biomechanical fragility were markedly reduced by increased bone resorption and decreased bone formation, and improved by the β-blocker propranolol at lower doses than those required to improve hypertension. Hypertension is often accompanied by enhanced sympathetic nerve activity and reduced bone mass.

Comprehensive investigation Rho may be necessary to understand the mutual relationship among calcium metabolism, bone metabolism, hypertension, and sympathetic nerve activity. Notably, sympathetic regulation of bone metabolism may be modified by sensory nervous activity, as described in this article. Although there is currently great interest in physiological modifications to signal transduction and the synaptic integrity of sympathetic and sensory neurons, further studies should clarify the mechanisms responsible for these modifications in peripheral nervous systems and give further insight into the neural regulation in bone metabolism. We are grateful to Shoko Imamura for excellent technical assistance.