Targeted expression of a dominant-negative N-cadherin in vivo delays peak bone mass and increases adipogenesis

Targeted expression of a dominant-negative N-cadherin in vivo delays peak bone mass and increases adipogenesis

Author Castro, Charlles Heldan de Moura Autor UNIFESP Google Scholar
Shin, Chan Soo Google Scholar
Stains, Joseph P. Google Scholar
Cheng, Su-Li Google Scholar
Sheikh, Sharmin Google Scholar
Mbalaviele, Gabriel Google Scholar
Szejnfeld, Vera Lucia Autor UNIFESP Google Scholar
Civitelli, Roberto Google Scholar
Institution Washington Univ
Universidade Federal de São Paulo (UNIFESP)
Seoul Natl Univ
Abstract We studied the function of osteoblast cadherins in vivo by transgenic expression of a truncated N-cadherin with dominant-negative action, driven by an osteoblast-specific promoter (OG2-NcadDeltaC). During the first 3 months of life, bone mineral density was reduced, whereas percent body fat was increased in transgenic animals compared with wild-type littermates, with associated decreased bone formation rate and osteoblast number, but normal osteoclast number. Osteoblast differentiation was delayed in calvaria cells isolated from transgenic mice. Likewise, the number of osteoblast precursors in bone marrow stromal cells from OG2-NcadDeltaC mice was decreased compared with wild-type cultures, whereas the number of adipogenic precursors was increased. in vitro, a transcriptionally active beta-catenin mutant reversed the delay in osteoblast differentiation and the exuberant adipogenesis. Thus, in vivo disruption of cadherin function hinders osteoblast differentiation and favors, indirectly, bone marrow progenitor cell commitment to the alternative adipogenic lineage via interference with beta-catenin signaling. This results in decreased bone formation, delayed acquisition of peak bone mass and increased body fat.
Keywords cell-cell adhesion
mesenchymal differentiation
transgenic mice
Language English
Date 2004-06-01
Published in Journal of Cell Science. Cambridge: Company of Biologists Ltd, v. 117, n. 13, p. 2853-2864, 2004.
ISSN 0021-9533 (Sherpa/Romeo, impact factor)
Publisher Company of Biologists Ltd
Extent 2853-2864
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000222650100021

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