Searching for additional endocrine functions of the skeleton: genetic approaches and implications for therapeutics

Our knowledge of whole organism physiology has greatly advanced in the past decades through mouse genetics. In particular, genetic studies have revealed that most organs interact with one another through hormones to maintain normal physiological functions and the homeostasis of the entire organism. Remarkably, through these studies, many unexpected novel endocrine means to regulate physiological functions have been uncovered. The skeletal system is one example. In this article, we review a series of studies that over the years have identified bone as an endocrine organ. The mechanism of action, pathological relevance and therapeutic implications of the functions of the bone-derived hormone osteocalcin are discussed. In the last part of this review, we discuss the possibility that additional endocrine functions of the skeleton may exist.