Transcription Factor Hematopoietically Expressed Homeobox Protein (Hhex) Negatively Regulates Osteoclast Differentiation by Controlling Cyclin-Dependent Kinase Inhibitors.

ABSTRACT: We investigated the role of hematopoietically expressed homeobox protein (Hhex) in osteoclast development. Trimethylation of lysine 27 of histone H3 at the cis-regulatory element of Hhex was maintained and that of lysine 4 was reduced during receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis, which was associated with a reduction of Hhex expression. Overexpression of Hhex in bone marrow-derived macrophages inhibited, whereas Hhex suppression promoted, RANKL-induced osteoclastogenesis in vitro. Conditional deletion of Hhex in osteoclast-lineage cells promoted osteoclastogenesis and reduced cancellous bone volume in mice, confirming the negative regulatory role of Hhex in osteoclast differentiation. Expression of cyclin

SUBMITTER: Watanabe H 

PROVIDER: S-EPMC9009129 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature