Bone tissue has been considered for a long time only as the effector of standing and movement as well as the main calcium deposit. Despite the historical view of bone as the final target of several hormones and hormone axis, recently it has been described that molecules produced by bone cells and released into the bloodstream are able to act paracrinally and endocrinologically on different cells and tissues and, hence, to explicate a biological effect. Particularly, circulating osteocalcin (OC), a osteoblast-derived vitamin K-dependent protein, seems to be involved, among other functions, in the regulation of glucose homeostasis at the pancreas and skeletal muscle level through the activation of the putative receptor, GPRC6A. Although many evidences about this mechanism have been obtained in rodents and in heterologous models expressing the murine receptor, the description of this signaling pathway in human is still lacking. Our studies are addressed at investigating the molecular effects of OC, in vitro, in human pancreatic β-cells. Parallel, we investigate, in collaboration with the Dept. of Biotechnology and Bioscences of the Università degli Studi di Milano-Bicocca (Prof. Laura Cipolla), the structural characteristics of the different forms of OC as well as their affinity for transmembrane proteins in selected cell types.

In collaboration with Prof. Sabrina Corbetta, Director of the Endocrinology Service of the IRCCS Istituto Ortopedico Galeazzi, we are also studying the bone-to-parathyroid axis and the role of the OC-GPRC6A signaling.