| First Author | McGee-Lawrence ME | Year | 2018 |
| Journal | J Cell Physiol | Volume | 233 |
| Issue | 4 | Pages | 2671-2680 |
| PubMed ID | 28840938 | Mgi Jnum | J:337659 |
| Mgi Id | MGI:6871434 | Doi | 10.1002/jcp.26148 |
| Citation | McGee-Lawrence ME, et al. (2018) Loss of Hdac3 in osteoprogenitors increases bone expression of osteoprotegerin, improving systemic insulin sensitivity. J Cell Physiol 233(4):2671-2680 |
| abstractText | Type 2 diabetes is an emerging global health epidemic. Foundations for new therapies are arising from understanding interactions between body systems. Bone-derived factors that reduce RANKL (receptor activator of NF-kappa B ligand) signaling in the liver may prevent insulin resistance and the onset of type 2 diabetes. Here we demonstrate that deletion of the epigenetic regulator, Hdac3, in Osx1-expressing osteoprogenitors prevents insulin resistance induced by high fat diet by increasing serum and skeletal gene expression levels of osteoprotegerin (Opg), a natural inhibitor of RANKL signaling. Removal of one Opg allele in mice lacking Hdac3 in Osx1+ osteoprogenitors increases the insulin resistance of the Hdac3-deficient mice on a high fat diet. Thus, Hdac3-depletion in osteoblasts increases expression of Opg, subsequently preserving insulin sensitivity. The Hdac inhibitor vorinostat also increased Opg transcription and histone acetylation of the Opg locus. These results define a new mechanism by which bone regulates systemic insulin sensitivity. |
