The CCN family member Wisp3, mutant in progressive pseudorheumatoid dysplasia, modulates BMP and Wnt signaling

ResearchWorks/Manakin Repository

Search ResearchWorks


Advanced Search

Browse

My Account

Statistics

Related Information

The CCN family member Wisp3, mutant in progressive pseudorheumatoid dysplasia, modulates BMP and Wnt signaling

Show simple item record

dc.contributor.author Nakamura, Yukio en_US
dc.contributor.author Weidinger, Gilbert en_US
dc.contributor.author Liang, Jennifer O. en_US
dc.contributor.author Aquilina-Beck, Allisan en_US
dc.contributor.author Tamai, Keiko en_US
dc.contributor.author Moon, Randall T. en_US
dc.contributor.author Warman, Matthew L. en_US
dc.date.accessioned 2010-04-21T15:59:03Z
dc.date.available 2010-04-21T15:59:03Z
dc.date.issued 2007-09-06 en_US
dc.identifier.citation Nakamura Y, Weidinger G, Liang JO, et al. The CCN family member Wisp3, mutant in progressive pseudorheumatoid dysplasia, modulates BMP and Wnt signaling. J Clin Invest. 2007;117(10):3075-3086. en_US
dc.identifier.other 10.1172/JCI32001 en_US
dc.identifier.uri http://www.jci.org/articles/view/32001 en_US
dc.identifier.uri http://hdl.handle.net/1773/15798
dc.description.abstract In humans, loss-of-function mutations in the gene encoding Wnt1 inducible signaling pathway protein 3 (WISP3) cause the autosomal-recessive skeletal disorder progressive pseudorheumatoid dysplasia (PPD). However, in mice there is no apparent phenotype caused by Wisp3 deficiency or overexpression. Consequently, the in vivo activities of Wisp3 have remained elusive. We cloned the zebrafish ortholog of Wisp3 and investigated its biologic activity in vivo using gain-of-function and loss-of-function approaches. Overexpression of zebrafish Wisp3 protein inhibited bone morphogenetic protein (BMP) and Wnt signaling in developing zebrafish. Conditioned medium–containing zebrafish and human Wisp3 also inhibited BMP and Wnt signaling in mammalian cells by binding to BMP ligand and to the Wnt coreceptors low-density lipoprotein receptor–related protein 6 (LRP6) and Frizzled, respectively. Wisp3 proteins containing disease-causing amino acid substitutions found in patients with PPD had reduced activity in these assays. Morpholino-mediated inhibition of zebrafish Wisp3 protein expression in developing zebrafish affected pharyngeal cartilage size and shape. These data provide a biologic assay for Wisp3, reveal a role for Wisp3 during zebrafish cartilage development, and suggest that dysregulation of BMP and/or Wnt signaling contributes to cartilage failure in humans with PPD. en_US
dc.language.iso en_US en_US
dc.title The CCN family member Wisp3, mutant in progressive pseudorheumatoid dysplasia, modulates BMP and Wnt signaling en_US


Files in this item

Files Size Format View
Nakamura1.pdf 1.513Mb PDF View/Open

This item appears in the following Collection(s)

Show simple item record