In an effort to determine whether bone has more functions than making bone we used clinical information as a way to forge a hypothesis testable in the mouse.
Specifically, we proposed that there should a coordinated regulation endocrine in nature of bone mass, energy, metabolism and reproduction. In testing all tenets of this hypothesis we showed that bone is an endocrine organ that, through the hormone osteocalcin regulates several aspects of energy metabolism at rest and during exercise, as well as male fertility. Moreover, this analysis revealed that unexpectedly, osteocalcin regulates many more physiological processes, and often does so by acting upstream of other regulatory molecules. Based on information gathered during our studies we asked whether osteocalcin could be an endocrine mediator of the maternal influence on the health of adult offspring. We also compared the respective roles of a glutamate transporter needed to activate osteocalcin, in the brain and in bone as a means to assess the importance of the skeleton as a regulator of central functions. Results of these ongoing investigations will be presented during the seminar. Altogether our work indicates that the appearance of bone during evolution has profoundly modified how many physiological functions are glutted and suggests that this knowledge could be harnessed to treat several age-related degenerative diseases.