| First Author | Ferron M | Year | 2015 |
| Journal | J Cell Biol | Volume | 208 |
| Issue | 6 | Pages | 761-76 |
| PubMed ID | 25753038 | Mgi Jnum | J:264734 |
| Mgi Id | MGI:6198390 | Doi | 10.1083/jcb.201409111 |
| Citation | Ferron M, et al. (2015) GGCX and VKORC1 inhibit osteocalcin endocrine functions. J Cell Biol 208(6):761-76 |
| abstractText | Osteocalcin (OCN) is an osteoblast-derived hormone favoring glucose homeostasis, energy expenditure, male fertility, brain development, and cognition. Before being secreted by osteoblasts in the bone extracellular matrix, OCN is gamma-carboxylated by the gamma-carboxylase (GGCX) on three glutamic acid residues, a cellular process requiring reduction of vitamin K (VK) by a second enzyme, a reductase called VKORC1. Although circumstantial evidence suggests that gamma-carboxylation may inhibit OCN endocrine functions, genetic evidence that it is the case is still lacking. Here we show using cell-specific gene inactivation models that gamma-carboxylation of OCN by GGCX inhibits its endocrine function. We further show that VKORC1 is required for OCN gamma-carboxylation in osteoblasts, whereas its paralogue, VKORC1L1, is dispensable for this function and cannot compensate for the absence of VKORC1 in osteoblasts. This study genetically and biochemically delineates the functions of the enzymes required for OCN modification and demonstrates that it is the uncarboxylated form of OCN that acts as a hormone. |
