Adenomatous Polyposis Coli-mediated Control of β-catenin is Essential for Both Chondrogenic and Osteogenic Differentiation of Skeletal Precursors

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Adenomatous Polyposis Coli-mediated Control of β-catenin is Essential for Both Chondrogenic and Osteogenic Differentiation of Skeletal Precursors

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dc.contributor.author Miclea, Razvan L
dc.contributor.author Karperien, Marcel
dc.contributor.author Bosch, Cathy AJ
dc.contributor.author van der Horst, Geertje
dc.contributor.author van der Valk, Martin A
dc.contributor.author Rawadi, Georges
dc.contributor.author Akçakaya, Pinar
dc.contributor.author Löwik, Clemens WGM
dc.contributor.author Fodde, Riccardo
dc.contributor.author Wit, Jan Maarten
dc.contributor.author Robanus-Maandag, Els C
dc.contributor.author Kobayashi, Tatsuya
dc.contributor.author Kronenberg, Henry Morris
dc.date.accessioned 2012-03-23T15:39:33Z
dc.date.issued 2009
dc.identifier.citation Miclea, Razvan L, Marcel Karperien, Cathy AJ Bosch, Geertje van der Horst, Martin A van der Valk, Tatsuya Kobayashi, Henry M Kronenberg. 2009. Adenomatous polyposis coli-mediated control of β-catenin is essential for both chondrogenic and osteogenic differentiation of skeletal precursors. BMC Developmental Biology 9: 26. en_US
dc.identifier.issn 1471-213X en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:8438182
dc.description.abstract Background: During skeletogenesis, protein levels of β-catenin in the canonical Wnt signaling pathway determine lineage commitment of skeletal precursor cells to osteoblasts and chondrocytes. Adenomatous polyposis coli (Apc) is a key controller of β-catenin turnover by down-regulating intracellular levels of β-catenin. Results: To investigate whether Apc is involved in lineage commitment of skeletal precursor cells, we generated conditional knockout mice lacking functional Apc in Col2a1-expressing cells. In contrast to other models in which an oncogenic variant of β-catenin was used, our approach resulted in the accumulation of wild type β-catenin protein due to functional loss of Apc. Conditional homozygous Apc mutant mice died perinatally showing greatly impaired skeletogenesis. All endochondral bones were misshaped and lacked structural integrity. Lack of functional Apc resulted in a pleiotropic skeletal cell phenotype. The majority of the precursor cells lacking Apc failed to differentiate into chondrocytes or osteoblasts. However, skeletal precursor cells in the proximal ribs were able to escape the noxious effect of functional loss of Apc resulting in formation of highly active osteoblasts. Inactivation of Apc in chondrocytes was associated with dedifferentiation of these cells. Conclusion: Our data indicate that a tight Apc-mediated control of β-catenin levels is essential for differentiation of skeletal precursors as well as for the maintenance of a chondrocytic phenotype in a spatio-temporal regulated manner. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.relation.isversionof doi://10.1186/1471-213X-9-26 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2678105/pdf/ en_US
dash.license LAA
dc.title Adenomatous Polyposis Coli-mediated Control of β-catenin is Essential for Both Chondrogenic and Osteogenic Differentiation of Skeletal Precursors en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal BMC Developmental Biology en_US
dash.depositing.author Kronenberg, Henry Morris
dc.date.available 2012-03-23T15:39:33Z
dash.affiliation.other HMS^Medicine-Massachusetts General Hospital en_US

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