{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nagano K"],"funding":["National Institute of Arthritis and Musculoskeletal and Skin Diseases","NIDCR NIH HHS","National Institute of Dental and Craniofacial Research","NIAMS NIH HHS"],"pagination":["e84171"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9681208"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11"],"pubmed_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, <i>Rspo3</i> haplo-insufficiency and <i>Rspo3</i> targeted deletion in <i>Runx2<sup>+</sup></i> 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 <i>Rspo3</i> deletion in osteoprogenitors results in the opposite phenot"],"journal":["eLife"],"pubmed_title":["R-spondin 3 deletion induces Erk phosphorylation to enhance Wnt signaling and promote bone formation in the appendicular skeleton."],"pmcid":["PMC9681208"],"funding_grant_id":["R01 AR064724","R01DE029615","R01 DE029615","R01AR064724"],"pubmed_authors":["Niehrs C","Yamana K","Saito H","Raval D","Kiviranta R","Nagano K","Pedroni AC","Gori F","Baron R"],"additional_accession":[]},"is_claimable":false,"name":"R-spondin 3 deletion induces Erk phosphorylation to enhance Wnt signaling and promote bone formation in the appendicular skeleton.","description":"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, <i>Rspo3</i> haplo-insufficiency and <i>Rspo3</i> targeted deletion in <i>Runx2<sup>+</sup></i> 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 <i>Rspo3</i> deletion in osteoprogenitors results in the opposite phenot","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2025-04-03T23:17:19.806Z","creation":"2024-11-20T03:54:39.74Z"},"accession":"S-EPMC9681208","cross_references":{"pubmed":["36321691"],"doi":["10.7554/eLife.84171"]}}