Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures.

ABSTRACT: The WNT16 locus is a major determinant of cortical bone thickness and nonvertebral fracture risk in humans. The disability, mortality and costs caused by osteoporosis-induced nonvertebral fractures are enormous. We demonstrate here that Wnt16-deficient mice develop spontaneous fractures as a result of low cortical thickness and high cortical porosity. In contrast, trabecular bone volume is not altered in these mice. Mechanistic studies revealed that WNT16 is osteoblast derived and inhibits human and mouse osteoclastogenesis both directly by acting on osteoclast progenitors and indirectly by increasing expression of osteoprotegerin (Opg) in osteoblasts. The signaling pathway activated by WNT16 in osteoclast progenitors is noncanonical, whereas the pathway activated in osteoblasts is both ca

SUBMITTER: Moverare-Skrtic S 

PROVIDER: S-EPMC4392888 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature