Osteocyte-specific WNT1 regulates osteoblast function during bone homeostasis

The brains of the bones: how osteocytes use WNT1 to control bone formation

“…Potential candidates for such a compensatory mechanism include WNT7b and WNT10b, which both enhance bone formation and interact with LRP5 (10, 11). Nevertheless, WNT1 seems to be the predominant WNT ligand in this context, as the results by Joeng et al show that anti-sclerostin treatment is unable to completely restitute bone mass in WNT1-deficient mice (9).…”

“…In this issue, Joeng et al set out to explore the mechanism whereby WNT1 determines bone mass (9). Previous observations from this group established that global loss of WNT1 causes low bone mass and fractures, but left open the question as to whether this phenotype was explained by the absence of functional WNT1 specifically in osteocytes.…”

“…Further mechanistic studies implicated an mTOR pathway in the control of osteoblasts through WNT1 (9). Overexpression of WNT1 in a stromal cell line accelerated osteoblast differentiation and increased mineralization in vitro, and this effect was diminished by rapamycin, which inhibits mTOR complex 1 (mTORC1) signaling.…”

“…Finally, Joeng et al showed that anti-sclerostin antibody treatment of the swaying mouse increased bone mass, improved mechanical bone properties, and decreased the fracture rate (9). These observed improvements in the swaying mouse following anti-sclerostin administration are significant on both mechanistic and translational levels.…”

Complex heterozygous <i>WNT1</i> mutation in severe recessive osteogenesis imperfecta of a Chinese patient

“…In vitro study showed that the WNT1 mutant interferes with the LPR5-mediated β-catenin signaling pathway, although the exact mechanism is currently unclear (7). Meanwhile, decreased mTORC1-dependent osteoblast function due to loss of WNT1 signaling in osteocytes is part of the reason for WNT1-related OI and osteoporosis according to mouse studies (11 not gain a substantial therapeutic effect using oral and intravenous bisphosphonate therapy, which is effective in OI patients with type I collagen mutations and anti-sclerostin antibody is a potential option for OI patient's treatment (11). Thus far, no more than 30 WNT1 mutations are identified and listed in the OI mutation database (6,7,9,(12)(13)(14)(15)(16)(17)(18).…”