Endocrine functions of bone and osteocalcinIt was discovered recently that bone functions not only as a scaffold for the rest of the body, but also as an endocrine organ. Bone cells secrete at least one hormone, osteocalcin, produced specifically by osteoblasts, which is implicated in the control of glucose metabolism. Our recent work has focused mainly on the regulation of osteocalcin activity by other hormones, including insulin, and the effect of osteocalcin on insulin secretion and insulin sensitivity. We are now interested in identifying and characterizing novel physiological and pathological roles of osteocalcin. We are also aiming to isolate additional bone-derived hormone(s), or “osteokines”, involved in bone endocrine function.
Physiological and pathological function of vitamin K and γ-carboxylationThe only known biological function of vitamin K is to serve as a co-factor for the γ-glutamyl carboxylase (GGCX), an enzyme responsible for the conversion of glutamic acid residues (GLU) into γ-carboxyglutamic acid (GLA) residues in specific secreted proteins. This posttranslational modification is found in some coagulation factors (prothrombin, factor IX, etc.), in MGP, a protein implicated in tissue mineralization, and in osteocalcin, a bone-derived hormone affecting glucose metabolism. However, we still don’t know all the γ-carboxylated proteins and their functions. Recent findings in humans and rodents suggest that vitamin K and γ-carboxylation may be involved in the control of energy metabolism and the development of obesity and diabetes. Our current goal is to address γ-carboxylation function in vivo through the generation of tissue-specific knockout mice for the enzymes implicated in this process. We are also planning to characterize, in a non-bias proteomic approach, the “γ-carboxylome” (i.e. identifying all the GLA proteins produced in tissues were the γ-glutamyl carboxylase is expressed).