{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:31:08Z","timestamp":1787167868340,"version":"build-2736575974"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Marie Sk\u0142odowska-Curie","award":["766347"],"award-info":[{"award-number":["766347"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Monogenic early onset osteoporosis (EOOP) is a rare disease defined by low bone mineral density (BMD) that results in increased risk of fracture in children and young adults. Although several causative genes have been identified, some of the EOOP causation remains unresolved. Whole-exome sequencing revealed a de novo heterozygous loss-of-function mutation in Wnt family member 11 (WNT11) (NM_004626.2:c.677_678dup p.Leu227Glyfs*22) in a 4-year-old boy with low BMD and fractures. We identified two heterozygous WNT11 missense variants (NM_004626.2:c.217G\u2009&amp;gt;\u2009A p.Ala73Thr) and (NM_004626.2:c.865G\u2009&amp;gt;\u2009A p.Val289Met) in a 51-year-old woman and in a 61-year-old woman, respectively, both with bone fragility. U2OS cells with heterozygous WNT11 mutation (NM_004626.2:c.690_721delfs*40) generated by CRISPR-Cas9 showed reduced cell proliferation (30%) and osteoblast differentiation (80%) as compared with wild-type U2OS cells. The expression of genes in the Wnt canonical and non-canonical pathways was inhibited in these mutant cells, but recombinant WNT11 treatment rescued the expression of Wnt pathway target genes. Furthermore, the expression of RSPO2, a WNT11 target involved in bone cell differentiation, and its receptor leucine-rich repeat containing G protein-coupled receptor 5 (LGR5), was decreased in WNT11 mutant cells. Treatment with WNT5A and WNT11 recombinant proteins reversed LGR5 expression, but Wnt family member 3A (WNT3A) recombinant protein treatment had no effect on LGR5 expression in mutant cells. Moreover, treatment with recombinant RSPO2 but not WNT11 or WNT3A activated the canonical pathway in mutant cells. In conclusion, we have identified WNT11 as a new gene responsible for EOOP, with loss-of-function variant inhibiting bone formation via Wnt canonical and non-canonical pathways. WNT11 may activate Wnt signaling by inducing the RSPO2\u2013LGR5 complex via the non-canonical Wnt pathway.<\/jats:p>","DOI":"10.1093\/hmg\/ddab349","type":"journal-article","created":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T15:11:56Z","timestamp":1638544316000},"page":"1622-1634","source":"Crossref","is-referenced-by-count":18,"title":["<i>WNT11,<\/i>\n                    a new gene associated with early onset osteoporosis, is required for osteoblastogenesis"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9044-7348","authenticated-orcid":false,"given":"Caroline","family":"Caetano da Silva","sequence":"first","affiliation":[{"name":"INSERM U1132 and Universit\u00e9 de Paris, Reference Centre for Rare Bone Diseases, Hospital Lariboisi\u00e8re, Paris F-75010, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9222-5009","authenticated-orcid":false,"given":"Thomas","family":"Edouard","sequence":"additional","affiliation":[{"name":"Endocrine Bone Diseases and Genetics Unit, Reference Centre for Rare Diseases of Calcium and Phosphate Metabolism, ERN BOND, OSCAR Network, Pediatric Clinical Research Unit, Children\u2019s Hospital, RESTORE INSERM U1301, Toulouse University Hospital, Toulouse 31300, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Fradin","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Clinique, Centre de R\u00e9f\u00e9rence des Anomalies du D\u00e9veloppement de l'Ouest, H\u00f4pital Sud de Rennes, Rennes F-35033, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Aubert-Mucca","sequence":"additional","affiliation":[{"name":"Endocrine Bone Diseases and Genetics Unit, Reference Centre for Rare Diseases of Calcium and Phosphate Metabolism, ERN BOND, OSCAR Network, Pediatric Clinical Research Unit, Children\u2019s Hospital, RESTORE INSERM U1301, Toulouse University Hospital, Toulouse 31300, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Ricquebourg","sequence":"additional","affiliation":[{"name":"INSERM U1132 and Universit\u00e9 de Paris, Reference Centre for Rare Bone Diseases, Hospital Lariboisi\u00e8re, Paris F-75010, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratish","family":"Raman","sequence":"additional","affiliation":[{"name":"Laboratory for Organogenesis and Regeneration (LOR), GIGA-Research, Li\u00e8ge University, Li\u00e8ge 4000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Pierre","family":"Salles","sequence":"additional","affiliation":[{"name":"Endocrine Bone Diseases and Genetics Unit, Reference Centre for Rare Diseases of Calcium and Phosphate Metabolism, ERN BOND, OSCAR Network, Pediatric Clinical Research Unit, Children\u2019s Hospital, RESTORE INSERM U1301, Toulouse University Hospital, Toulouse 31300, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Charon","sequence":"additional","affiliation":[{"name":"Department of Radiology, CHU de Rennes, Rennes F-35000, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Guggenbuhl","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, CHU de Rennes, Rennes F-35000, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Muller","sequence":"additional","affiliation":[{"name":"Laboratory for Organogenesis and Regeneration (LOR), GIGA-Research, Li\u00e8ge University, Li\u00e8ge 4000, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Cohen-Solal","sequence":"additional","affiliation":[{"name":"INSERM U1132 and Universit\u00e9 de Paris, Reference Centre for Rare Bone Diseases, Hospital Lariboisi\u00e8re, Paris F-75010, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Collet","sequence":"additional","affiliation":[{"name":"INSERM U1132 and Universit\u00e9 de Paris, Reference Centre for Rare Bone Diseases, Hospital Lariboisi\u00e8re, Paris F-75010, France"},{"name":"D\u00e9partement de G\u00e9n\u00e9tique, UF de G\u00e9n\u00e9tique Mol\u00e9culaire, H\u00f4pital Robert Debr\u00e9, APHP, Paris F-75019, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,7]]},"reference":[{"key":"2022052023335647000_ref1","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/BF01623944","article-title":"The genetics of proximal femur geometry, distribution of bone mass and bone mineral density","volume":"6","author":"Slemenda","year":"1996","journal-title":"Osteoporos. Int."},{"key":"2022052023335647000_ref2","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1002\/jbmr.5650101223","article-title":"Segregation analysis and variance components analysis of bone mineral density in healthy families","volume":"10","author":"Gu\u00e9guen","year":"1995","journal-title":"J. Bone Miner. Res."},{"key":"2022052023335647000_ref3","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3389\/fendo.2019.00337","article-title":"Recent advances in the genetics of fractures in osteoporosis","volume":"10","author":"Koromani","year":"2019","journal-title":"Front. Endocrinol."},{"key":"2022052023335647000_ref4","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.bone.2018.06.001","article-title":"Genome-wide association study of extreme high bone mass: contribution of common genetic variation to extreme BMD phenotypes and potential novel BMD-associated genes","volume":"114","author":"Gregson","year":"2018","journal-title":"Bone"},{"key":"2022052023335647000_ref5","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/s41588-018-0302-x","article-title":"An atlas of genetic influences on osteoporosis in humans and mice","volume":"51","author":"Morris","year":"2019","journal-title":"Nat. Genet."},{"key":"2022052023335647000_ref6","doi-asserted-by":"crossref","first-page":"e1003152","DOI":"10.1371\/journal.pmed.1003152","article-title":"Development of a polygenic risk score to improve screening for fracture risk: a genetic risk prediction study","volume":"17","author":"Forgetta","year":"2020","journal-title":"PLoS Med."},{"key":"2022052023335647000_ref7","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/jbm4.10020","article-title":"Primary osteoporosis in young adults: genetic basis and identification of novel variants in causal genes","volume":"2","author":"Collet","year":"2017","journal-title":"JBMR Plus"},{"key":"2022052023335647000_ref8","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1002\/jbmr.3959","article-title":"Biomarkers in WNT1 and PLS3 osteoporosis: altered concentrations of DKK1 and FGF23","volume":"35","author":"M\u00e4kitie","year":"2020","journal-title":"J. Bone Miner. 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Med."},{"key":"2022052023335647000_ref12","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/jbmr.4197","article-title":"Clinical phenotype and relevance of LRP5 and LRP6 variants in patients with early-onset osteoporosis (EOOP)","volume":"36","author":"St\u00fcrznickel","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"2022052023335647000_ref13","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nm.3074","article-title":"WNT signaling in bone homeostasis and disease: from human mutations to treatments","volume":"19","author":"Baron","year":"2013","journal-title":"Nat. Med."},{"key":"2022052023335647000_ref14","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3389\/fendo.2020.00165","article-title":"WNT Signaling and bone: lessons from skeletal dysplasias and disorders","volume":"11","author":"Huybrechts","year":"2020","journal-title":"Front. Endocrinol."},{"key":"2022052023335647000_ref15","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1172\/JCI28551","article-title":"Regulation of bone mass by Wnt signaling","volume":"116","author":"Krishnan","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2022052023335647000_ref16","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s00774-009-0064-8","article-title":"Wnt signaling in bone metabolism","volume":"27","author":"Kubota","year":"2009","journal-title":"J. Bone Miner. Metab."},{"key":"2022052023335647000_ref17","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nm.2653","article-title":"Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis","volume":"18","author":"Maeda","year":"2012","journal-title":"Nat. Med."},{"key":"2022052023335647000_ref18","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1083\/jcb.201008012","article-title":"Control of bone formation by the serpentine receptor Frizzled-9","volume":"192","author":"Albers","year":"2011","journal-title":"J. Cell Biol."},{"key":"2022052023335647000_ref19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ydbio.2013.02.024","article-title":"Different thresholds of Wnt-frizzled 7 signaling coordinate proliferation, morphogenesis and fate of endoderm progenitor cells","volume":"378","author":"Zhang","year":"2013","journal-title":"Dev. Biol."},{"key":"2022052023335647000_ref20","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1359\/JBMR.040807","article-title":"Secreted frizzled-related protein-1 inhibits RANKL-dependent osteoclast formation","volume":"19","author":"H\u00e4usler","year":"2004","journal-title":"J. Bone Miner. Res."},{"key":"2022052023335647000_ref21","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1101\/gad.235473.113","article-title":"The R-spondin\/Lgr5\/Rnf43 module: regulator of Wnt signal strength","volume":"28","author":"Lau","year":"2014","journal-title":"Genes Dev."},{"key":"2022052023335647000_ref22","first-page":"REVIEWS3001","article-title":"The Wnts","volume":"3","author":"Miller","year":"2002","journal-title":"Genome Biol."},{"key":"2022052023335647000_ref23","doi-asserted-by":"crossref","first-page":"e1681","DOI":"10.1002\/mgg3.1681","article-title":"More severe phenotype of early-onset osteoporosis associated with recessive form of LRP5 and combination with DKK1 or WNT3A","volume":"9","author":"Caetano da Silva","year":"2021","journal-title":"Mol. Genet. Genomic Med."},{"key":"2022052023335647000_ref24","doi-asserted-by":"crossref","first-page":"101118","DOI":"10.1016\/j.bonr.2021.101118","article-title":"Heterozygous variant in WNT1 gene in two brothers with early onset osteoporosis","volume":"15","author":"Turin","year":"2021","journal-title":"Bone Rep."},{"key":"2022052023335647000_ref25","first-page":"1","article-title":"Comprehensive genetic analysis of 128 candidate genes in a cohort with idiopathic, severe, or familial osteoporosis","volume":"4","author":"Rocha-Braz","year":"2020","journal-title":"JES"},{"key":"2022052023335647000_ref26","article-title":"Early-onset osteoporosis","author":"M\u00e4kitie","year":"2021","journal-title":"Calcif. Tissue Int."},{"key":"2022052023335647000_ref27","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1111\/j.1748-1716.2011.02297.x","article-title":"Wnt11 in 2011 \u2013 the regulation and function of a non-canonical Wnt","volume":"204","author":"Uysal-Onganer","year":"2012","journal-title":"Acta Physiol."},{"key":"2022052023335647000_ref28","doi-asserted-by":"crossref","first-page":"8588","DOI":"10.1038\/s41598-018-26901-8","article-title":"Role of Wnt11 during osteogenic differentiation of human mesenchymal stem cells on microstructured titanium surfaces","volume":"8","author":"Boyan","year":"2018","journal-title":"Sci. Rep."},{"key":"2022052023335647000_ref29","doi-asserted-by":"crossref","first-page":"14117","DOI":"10.1074\/jbc.M808337200","article-title":"Wnt11 promotes osteoblast maturation and mineralization through R-spondin 2","volume":"284","author":"Friedman","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2022052023335647000_ref30","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0378-1119(98)00393-X","article-title":"Isolation, characterisation and embryonic expression of WNT11, a gene which maps to 11q13.5 and has possible roles in the development of skeleton, kidney and lung","volume":"219","author":"Lako","year":"1998","journal-title":"Gene"},{"key":"2022052023335647000_ref31","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"2022052023335647000_ref32","doi-asserted-by":"crossref","first-page":"e94904","DOI":"10.1172\/jci.insight.94904","article-title":"Wnt11 regulates cardiac chamber development and disease during perinatal maturation","volume":"2","author":"Touma","year":"2017","journal-title":"JCI Insight."},{"key":"2022052023335647000_ref33","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ydbio.2014.11.005","article-title":"Mapping the dynamic expression of Wnt11 and the lineage contribution of Wnt11-expressing cells during early mouse development","volume":"398","author":"Sinha","year":"2015","journal-title":"Dev. Biol."},{"key":"2022052023335647000_ref34","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ydbio.2004.12.013","article-title":"Wnt11-R, a protein closely related to mammalian Wnt11, is required for heart morphogenesis in Xenopus","volume":"279","author":"Garriock","year":"2005","journal-title":"Dev. Biol."},{"key":"2022052023335647000_ref35","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/35011068","article-title":"Silberblick\/Wnt11 mediates convergent extension movements during zebrafish gastrulation","volume":"405","author":"Heisenberg","year":"2000","journal-title":"Nature"},{"key":"2022052023335647000_ref36","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1006\/dbio.1997.8511","article-title":"The function of silberblick in the positioning of the eye anlage in the zebrafish embryo","volume":"184","author":"Heisenberg","year":"1997","journal-title":"Dev. Biol."},{"key":"2022052023335647000_ref37","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa1215458","article-title":"WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta","volume":"368","author":"Laine","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"2022052023335647000_ref38","doi-asserted-by":"crossref","first-page":"9462","DOI":"10.1002\/jcb.27262","article-title":"Wnt11 promotes BMP9-induced osteogenic differentiation through BMPs\/Smads and p38 MAPK in mesenchymal stem cells","volume":"119","author":"Zhu","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"2022052023335647000_ref39","doi-asserted-by":"crossref","first-page":"21520","DOI":"10.1038\/srep21520","article-title":"Induction of WNT11 by hypoxia and hypoxia-inducible factor-1\u03b1 regulates cell proliferation, migration and invasion","volume":"6","author":"Mori","year":"2016","journal-title":"Sci. Rep."},{"key":"2022052023335647000_ref40","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1038\/s41374-019-0277-y","article-title":"Ascl1-induced Wnt11 regulates neuroendocrine differentiation, cell proliferation, and E-cadherin expression in small-cell lung cancer and Wnt11 regulates small-cell lung cancer biology","volume":"99","author":"Tenjin","year":"2019","journal-title":"Lab. Investig."},{"key":"2022052023335647000_ref41","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1002\/jbm.a.36846","article-title":"Primary osteoblasts, osteoblast precursor cells or osteoblast-like cell lines: which human cell types are (most) suitable for characterizing 45S5-bioactive glass?","volume":"108","author":"Wilkesmann","year":"2020","journal-title":"J. Biomed. Mater. Res. A"},{"key":"2022052023335647000_ref42","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.bone.2019.06.027","article-title":"Aberrant activation of Wnt signaling pathway altered osteocyte mineralization","volume":"127","author":"Zhou","year":"2019","journal-title":"Bone"},{"key":"2022052023335647000_ref43","doi-asserted-by":"crossref","first-page":"24659","DOI":"10.1074\/jbc.M311724200","article-title":"Multiple mechanisms for Wnt11-mediated repression of the canonical Wnt signaling pathway","volume":"279","author":"Maye","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2022052023335647000_ref44","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ydbio.2014.11.015","article-title":"Wnt5a and Wnt11 inhibit the canonical Wnt pathway and promote cardiac progenitor development via the caspase-dependent degradation of AKT","volume":"398","author":"Bisson","year":"2015","journal-title":"Dev. Biol."},{"key":"2022052023335647000_ref45","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ydbio.2012.06.020","article-title":"Wnt5a can both activate and repress Wnt\/\u03b2-catenin signaling during mouse embryonic development","volume":"369","author":"Amerongen","year":"2012","journal-title":"Dev. Biol."},{"key":"2022052023335647000_ref46","doi-asserted-by":"crossref","first-page":"10239","DOI":"10.18632\/oncotarget.3518","article-title":"WNT5A promotes stemness characteristics in nasopharyngeal carcinoma cells leading to metastasis and tumorigenesis","volume":"6","author":"Qin","year":"2015","journal-title":"Oncotarget"},{"key":"2022052023335647000_ref47","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s00018-015-2076-y","article-title":"WNT-5A: signaling and functions in health and disease","volume":"73","author":"Kumawat","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"2022052023335647000_ref48","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1128\/MCB.22.4.1172-1183.2002","article-title":"Wnt\/beta-catenin\/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway","volume":"22","author":"Jho","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"2022052023335647000_ref49","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/nm.3654","article-title":"Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures","volume":"20","author":"Mov\u00e9rare-Skrtic","year":"2014","journal-title":"Nat. Med."},{"key":"2022052023335647000_ref50","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/embor.2011.175","article-title":"LGR4 and LGR5 are R-spondin receptors mediating Wnt\/\u03b2-catenin and Wnt\/PCP signalling","volume":"12","author":"Glinka","year":"2011","journal-title":"EMBO Rep."},{"key":"2022052023335647000_ref51","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nature10337","article-title":"Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling","volume":"476","author":"Lau","year":"2011","journal-title":"Nature"},{"key":"2022052023335647000_ref52","doi-asserted-by":"crossref","first-page":"e37137","DOI":"10.1371\/journal.pone.0037137","article-title":"LGR6 is a high affinity receptor of R-spondins and potentially functions as a tumor suppressor","volume":"7","author":"Gong","year":"2012","journal-title":"PLoS One"},{"key":"2022052023335647000_ref53","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41413-018-0026-7","article-title":"R-spondin-2 is a Wnt agonist that regulates osteoblast activity and bone mass","volume":"6","author":"Knight","year":"2018","journal-title":"Bone Res."},{"key":"2022052023335647000_ref54","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1016\/j.biocel.2012.09.006","article-title":"The R-spondin family of proteins: emerging regulators of WNT signaling","volume":"44","author":"Jin","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"2022052023335647000_ref55","doi-asserted-by":"crossref","first-page":"e0180711","DOI":"10.1371\/journal.pone.0180711","article-title":"Alteration of Wnt5a expression and of the non-canonical Wnt\/PCP and Wnt\/PKC-Ca2+ pathways in human osteoarthritis osteoblasts","volume":"12","author":"Martineau","year":"2017","journal-title":"PLoS One"},{"key":"2022052023335647000_ref56","first-page":"247","article-title":"Pediatric data for dual X-ray absorptiometric measures of normal lumbar bone mineral density in children under 5 years of age using the lunar prodigy densitometer","volume":"16","author":"Manousaki","year":"2016","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"2022052023335647000_ref57","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1006\/geno.1996.0614","article-title":"Sensitivity and selectivity in protein similarity searches: a comparison of Smith-waterman in hardware to BLAST and FASTA","volume":"38","author":"Shpaer","year":"1996","journal-title":"Genomics"},{"key":"2022052023335647000_ref58","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with burrows-wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2022052023335647000_ref59","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"2022052023335647000_ref60","doi-asserted-by":"crossref","first-page":"e2974","DOI":"10.1038\/cddis.2017.366","article-title":"Uev1A facilitates osteosarcoma differentiation by promoting Smurf1-mediated Smad1 ubiquitination and degradation","volume":"8","author":"Zhang","year":"2017","journal-title":"Cell Death Dis."}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/advance-article-pdf\/doi\/10.1093\/hmg\/ddab349\/42198713\/ddab349.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/31\/10\/1622\/43755146\/ddab349.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/31\/10\/1622\/43755146\/ddab349.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T19:35:06Z","timestamp":1653075306000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/31\/10\/1622\/6454974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,7]]},"references-count":60,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,12,7]]},"published-print":{"date-parts":[[2022,5,19]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddab349","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,5,15]]},"published":{"date-parts":[[2021,12,7]]}}}