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

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

DSpace/Manakin Repository

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

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