Catenins: role in the functioning of the skeleton as an endocrine organ?

Diseases such as diabetes, obesity and osteoporosis involve complex effects on multiple organ systems. Manifestations in these pathophysiological conditions underscore the regular association between impaired energy metabolism and reduced bone mass and increased bone marrow adiposity, emphasizing the significance of the interactions between the classical metabolic tissues, bone and bone marrow fat. Evidence indicates that the skeleton represents an endocrine organ integrated in whole-body physiology as an important contributor to the regulation of systemic energy homeostasis, through hormonal functions exerted by both osteoblasts and marrow adipocytes. Our preliminary data indicate that p120- and a-E-catenin, two molecules involved in cell adhesion, may play critical roles in cell fate determination of skeletal progenitors, and in the control of bone formation, marrow fat accumulation, and systemic energy metabolism. The current study is designed to address the cellular and molecular mechanisms by which the functioning of these molecules in skeletal progenitors may modulate the complex endocrine network of bone and the regulation of systemic energy metabolism. Results from this work will bring new insights in key biological processes that determine bone mass and will help elucidating the functional significance of marrow adipose tissue and skeletal integrity in the endocrine role of the skeleton, which may have important impact in the control of widespread metabolic diseases.