Mechanisms Mediating Changes in Central Regulation of Bone Mass (R01)

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Purpose This FOA issued by the National Institute on Aging (NIA), National Institutes of Health (NIH), solicits Research Project Grant (R01) applications from institutions/ organizations that propose to investigate neural, neuroendocrine and/or related integrative physiological mechanisms that mediate age dependent changes in bone metabolism and health. The discovery that leptin, secreted by adipocytes, regulates bone mass through a central relay involving serotonergic neurons has generated considerable interest and raised many additional questions about the identity of neural mediator(s) linking the brain to skeletal physiology as well as the potential involvement of other factors whether they be neural/hypothalamic factors (Serotonin, TSH and FSH, ephrins, dynorphins, endocannabiniods/receptors) or other factors such as ACTH, as well as distant tissues/organs such as adipose tissue) in regulating bone mass as well as distant tissues/organs. In addition, recent reports indicate that direct innervations are important in mechanical load sensing and bone remodeling. Furthermore, in view of the well documented age-related changes in neuroendocrine activity, this emerging field of research will significantly reshape our understanding of mechanisms modulating age-related changes in bone mass (increase or decrease in bone mass and/or the etiology of osteoporosis). We are interested in studies to identify and characterize age-related changes in these factors that serve to integrate activity influencing bone mass as well as integrative cross talk mechanisms (neural, endocrine, immune or novel) that coordinate these signaling pathways. Mechanism of Support. This FOA will utilize the R01 grant mechanism. Funds Available and Anticipated Number of Awards NIA will fund 3-5 applications with annual budgets up to and including $250,000 in direct costs for up to 5 years depending upon receipt of an adequate number of meritorious applications.

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