Genetic inhibition of PPARγ S112 phosphorylation reduces bone formation and stimulates marrow adipogenesis.

ABSTRACT: A common feature of many skeletal diseases is the accumulation of marrow fat. A reciprocal relationship exists between osteogenesis and adipogenesis in bone marrow that is mediated by the relative activity of PPARγ and RUNX2 transcription factors. The ERK/MAPK pathway is an important inducer of MSC differentiation to osteoblasts and an inhibitor of adipogenesis that functions by phosphorylating RUNX2 and PPARγ. To begin to assess the importance of this regulation in vivo, we examined the consequences of blocking one arm of this pathway, PPARγ S112 phosphorylation, by evaluating the bone phenotype of PPARγ S112A mutant mice. This mutation prevents MAPK phosphorylation and inhibition of PPARγ transcriptional activity. Both male and female PPARγ S112A mice had decreased tibial and vertebral B

SUBMITTER: Ge C 

PROVIDER: S-EPMC5743762 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature