Sfrp4 repression of the Ror2/Jnk cascade in osteoclasts protects cortical bone from excessive endosteal resorption.

ABSTRACT: Loss-of-function mutations in the Wnt inhibitor secreted frizzled receptor protein 4 (SFRP4) cause Pyle's disease (OMIM 265900), a rare skeletal disorder characterized by wide metaphyses, significant thinning of cortical bone, and fragility fractures. In mice, we have shown that the cortical thinning seen in the absence of Sfrp4 is associated with decreased periosteal and endosteal bone formation and increased endocortical resorption. While the increase in Rankl/Opg in cortical bone of mice lacking Sfrp4 suggests an osteoblast-dependent effect on endocortical osteoclast (OC) activity, whether Sfrp4 can cell-autonomously affect OCs is not known. We found that Sfrp4 is expressed during bone marrow macrophage OC differentiation and that Sfrp4 significantly suppresses the

SUBMITTER: Chen K 

PROVIDER: S-EPMC6628642 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature