Matches in SemOpenAlex for { <https://semopenalex.org/work/W4307967508> ?p ?o ?g. }
- W4307967508 abstract "Activation of Wnt signaling leads to high bone density. The R-spondin family of four secreted glycoproteins (Rspo1-4) amplifies Wnt signaling. In humans, RSPO3 variants are strongly associated with bone density. Here, we investigated the role of Rspo3 in skeletal homeostasis in mice. Using a comprehensive set of mouse genetic and mechanistic studies, we show that in the appendicular skeleton, Rspo3 haplo-insufficiency and Rspo3 targeted deletion in Runx2+ osteoprogenitors lead to an increase in trabecular bone mass, with increased number of osteoblasts and bone formation. In contrast and highlighting the complexity of Wnt signaling in the regulation of skeletal homeostasis, we show that Rspo3 deletion in osteoprogenitors results in the opposite phenotype in the axial skeleton, i.e., low vertebral trabecular bone mass. Mechanistically, Rspo3 deficiency impairs the inhibitory effect of Dkk1 on Wnt signaling activation and bone mass. We demonstrate that Rspo3 deficiency leads to activation of Erk signaling which in turn, stabilizes β-catenin and Wnt signaling activation. Our data demonstrate that Rspo3 haplo-insufficiency/deficiency boosts canonical Wnt signaling by activating Erk signaling, to favor osteoblastogenesis, bone formation, and bone mass." @default.
- W4307967508 created "2022-11-06" @default.
- W4307967508 creator A5001613323 @default.
- W4307967508 creator A5006803961 @default.
- W4307967508 creator A5040113122 @default.
- W4307967508 creator A5049894537 @default.
- W4307967508 creator A5053072500 @default.
- W4307967508 creator A5055182095 @default.
- W4307967508 creator A5071603809 @default.
- W4307967508 creator A5080707920 @default.
- W4307967508 creator A5087404117 @default.
- W4307967508 date "2022-11-02" @default.
- W4307967508 modified "2023-09-26" @default.
- W4307967508 title "R-spondin 3 deletion induces Erk phosphorylation to enhance Wnt signaling and promote bone formation in the appendicular skeleton" @default.
- W4307967508 cites W1865110278 @default.
- W4307967508 cites W1969070584 @default.
- W4307967508 cites W1981020155 @default.
- W4307967508 cites W1983179515 @default.
- W4307967508 cites W1984220883 @default.
- W4307967508 cites W1984543735 @default.
- W4307967508 cites W1993913554 @default.
- W4307967508 cites W1996300988 @default.
- W4307967508 cites W2001636656 @default.
- W4307967508 cites W2002423017 @default.
- W4307967508 cites W2006419043 @default.
- W4307967508 cites W2010217881 @default.
- W4307967508 cites W2011203192 @default.
- W4307967508 cites W2019196925 @default.
- W4307967508 cites W2020903392 @default.
- W4307967508 cites W2022080291 @default.
- W4307967508 cites W2023123202 @default.
- W4307967508 cites W2024213821 @default.
- W4307967508 cites W2027150010 @default.
- W4307967508 cites W2033585269 @default.
- W4307967508 cites W2037978897 @default.
- W4307967508 cites W2056278417 @default.
- W4307967508 cites W2060117171 @default.
- W4307967508 cites W2065766094 @default.
- W4307967508 cites W2066749771 @default.
- W4307967508 cites W2078060536 @default.
- W4307967508 cites W2082618349 @default.
- W4307967508 cites W2082981899 @default.
- W4307967508 cites W2090135807 @default.
- W4307967508 cites W2090915792 @default.
- W4307967508 cites W2096425957 @default.
- W4307967508 cites W2097556510 @default.
- W4307967508 cites W2101095306 @default.
- W4307967508 cites W2101276491 @default.
- W4307967508 cites W2107277218 @default.
- W4307967508 cites W2123627492 @default.
- W4307967508 cites W2124873014 @default.
- W4307967508 cites W2136426180 @default.
- W4307967508 cites W2139133092 @default.
- W4307967508 cites W2149682914 @default.
- W4307967508 cites W2150856909 @default.
- W4307967508 cites W2155040292 @default.
- W4307967508 cites W2159189366 @default.
- W4307967508 cites W2160664367 @default.
- W4307967508 cites W2171977041 @default.
- W4307967508 cites W2192080449 @default.
- W4307967508 cites W2344880307 @default.
- W4307967508 cites W2404285912 @default.
- W4307967508 cites W2468098983 @default.
- W4307967508 cites W2475138245 @default.
- W4307967508 cites W2527406818 @default.
- W4307967508 cites W2591100740 @default.
- W4307967508 cites W2621361823 @default.
- W4307967508 cites W2726890026 @default.
- W4307967508 cites W2771054454 @default.
- W4307967508 cites W2785595329 @default.
- W4307967508 cites W2800557466 @default.
- W4307967508 cites W2803820523 @default.
- W4307967508 cites W2886649414 @default.
- W4307967508 cites W2901588898 @default.
- W4307967508 cites W2936978550 @default.
- W4307967508 cites W2938096285 @default.
- W4307967508 cites W2941896347 @default.
- W4307967508 cites W2953442647 @default.
- W4307967508 cites W3003574179 @default.
- W4307967508 cites W3015428855 @default.
- W4307967508 cites W3095635070 @default.
- W4307967508 cites W3133551726 @default.
- W4307967508 cites W3191335158 @default.
- W4307967508 cites W4207083034 @default.
- W4307967508 cites W4211130907 @default.
- W4307967508 cites W4255492705 @default.
- W4307967508 doi "https://doi.org/10.7554/elife.84171" @default.
- W4307967508 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36321691" @default.
- W4307967508 hasPublicationYear "2022" @default.
- W4307967508 type Work @default.
- W4307967508 citedByCount "0" @default.
- W4307967508 crossrefType "journal-article" @default.
- W4307967508 hasAuthorship W4307967508A5001613323 @default.
- W4307967508 hasAuthorship W4307967508A5006803961 @default.
- W4307967508 hasAuthorship W4307967508A5040113122 @default.
- W4307967508 hasAuthorship W4307967508A5049894537 @default.
- W4307967508 hasAuthorship W4307967508A5053072500 @default.
- W4307967508 hasAuthorship W4307967508A5055182095 @default.
- W4307967508 hasAuthorship W4307967508A5071603809 @default.
- W4307967508 hasAuthorship W4307967508A5080707920 @default.