DC Field | Value | Language |
---|---|---|
dc.contributor.author | Wei, Wei | ko |
dc.contributor.author | Zeve, Daniel | ko |
dc.contributor.author | Suh, Jae Myoung | ko |
dc.contributor.author | Wang, Xueqian | ko |
dc.contributor.author | Du, Yang | ko |
dc.contributor.author | Zerwekh, Joseph E. | ko |
dc.contributor.author | Dechow, Paul C. | ko |
dc.contributor.author | Graff, Jonathan M. | ko |
dc.contributor.author | Wan, Yihong | ko |
dc.date.accessioned | 2015-04-29T01:20:11Z | - |
dc.date.available | 2015-04-29T01:20:11Z | - |
dc.date.created | 2015-04-24 | - |
dc.date.created | 2015-04-24 | - |
dc.date.issued | 2011-12 | - |
dc.identifier.citation | MOLECULAR AND CELLULAR BIOLOGY, v.31, no.23, pp.4706 - 4719 | - |
dc.identifier.issn | 0270-7306 | - |
dc.identifier.uri | http://hdl.handle.net/10203/198272 | - |
dc.description.abstract | Wnt/beta-catenin signaling is a critical regulator of skeletal physiology. However, previous studies have mainly focused on its roles in osteoblasts, while its specific function in osteoclasts is unknown. This is a clinically important question because neutralizing antibodies against Wnt antagonists are promising new drugs for bone diseases. Here, we show that in osteoclastogenesis, beta-catenin is induced during the macrophage colony-stimulating factor (M-CSF)-mediated quiescence-to-proliferation switch but suppressed during the RANKL-mediated proliferation-to-differentiation switch. Genetically, beta-catenin deletion blocks osteoclast precursor proliferation, while beta-catenin constitutive activation sustains proliferation but prevents osteoclast differentiation, both causing osteopetrosis. In contrast, beta-catenin heterozygosity enhances osteoclast differentiation, causing osteoporosis. Biochemically, Wnt activation attenuates whereas Wnt inhibition stimulates osteoclastogenesis. Mechanistically, beta-catenin activation increases GATA2/Evi1 expression but abolishes RANKL-induced c-Jun phosphorylation. Therefore, beta-catenin exerts a pivotal biphasic and dosage-dependent regulation of osteoclastogenesis. Importantly, these findings suggest that Wnt activation is a more effective treatment for skeletal fragility than previously recognized that confers dual anabolic and anti-catabolic benefits. | - |
dc.language | English | - |
dc.publisher | AMER SOC MICROBIOLOGY | - |
dc.subject | ACTIVATED RECEPTOR-GAMMA | - |
dc.subject | INCREASES BONE-FORMATION | - |
dc.subject | STEM-CELLS | - |
dc.subject | OSTEOPROTEGERIN LIGAND | - |
dc.subject | SCLEROSTIN ANTIBODY | - |
dc.subject | MULTIPLE-MYELOMA | - |
dc.subject | C-JUN | - |
dc.subject | WNT | - |
dc.subject | DIFFERENTIATION | - |
dc.subject | MICE | - |
dc.title | Biphasic and Dosage-Dependent Regulation of Osteoclastogenesis by beta-Catenin | - |
dc.type | Article | - |
dc.identifier.wosid | 000296791900005 | - |
dc.type.rims | ART | - |
dc.citation.volume | 31 | - |
dc.citation.issue | 23 | - |
dc.citation.beginningpage | 4706 | - |
dc.citation.endingpage | 4719 | - |
dc.citation.publicationname | MOLECULAR AND CELLULAR BIOLOGY | - |
dc.identifier.doi | 10.1128/MCB.05980-11 | - |
dc.contributor.localauthor | Suh, Jae Myoung | - |
dc.contributor.nonIdAuthor | Wei, Wei | - |
dc.contributor.nonIdAuthor | Zeve, Daniel | - |
dc.contributor.nonIdAuthor | Wang, Xueqian | - |
dc.contributor.nonIdAuthor | Du, Yang | - |
dc.contributor.nonIdAuthor | Zerwekh, Joseph E. | - |
dc.contributor.nonIdAuthor | Dechow, Paul C. | - |
dc.contributor.nonIdAuthor | Graff, Jonathan M. | - |
dc.contributor.nonIdAuthor | Wan, Yihong | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | ACTIVATED RECEPTOR-GAMMA | - |
dc.subject.keywordPlus | INCREASES BONE-FORMATION | - |
dc.subject.keywordPlus | STEM-CELLS | - |
dc.subject.keywordPlus | OSTEOPROTEGERIN LIGAND | - |
dc.subject.keywordPlus | SCLEROSTIN ANTIBODY | - |
dc.subject.keywordPlus | MULTIPLE-MYELOMA | - |
dc.subject.keywordPlus | C-JUN | - |
dc.subject.keywordPlus | WNT | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.subject.keywordPlus | MICE | - |
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