TY - JOUR
T1 - Targeted expression of a dominant-negative N-cadherin in vivo delays peak bone mass and increases adipogenesis
AU - Castro, Charlles H.M.
AU - Shin, Chan Soo
AU - Stains, Joseph P.
AU - Cheng, Su Li
AU - Sheikh, Sharmin
AU - Mbalaviele, Gabriele
AU - Szejnfeld, Vera Lucia
AU - Civitelli, Roberto
PY - 2004/6/1
Y1 - 2004/6/1
N2 - 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-NcadΔC). 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-NcadΔC mice was decreased compared with wild-type cultures, whereas the number of adipogenic precursors was increased. In vitro, a transcriptionally active β-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 β-catenin signaling. This results in decreased bone formation, delayed acquisition of peak bone mass and increased body fat.
AB - 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-NcadΔC). 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-NcadΔC mice was decreased compared with wild-type cultures, whereas the number of adipogenic precursors was increased. In vitro, a transcriptionally active β-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 β-catenin signaling. This results in decreased bone formation, delayed acquisition of peak bone mass and increased body fat.
KW - Adipogenesis
KW - Cadherins
KW - Cell-cell adhesion
KW - Mesenchymal differentiation
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=3242883440&partnerID=8YFLogxK
U2 - 10.1242/jcs.01133
DO - 10.1242/jcs.01133
M3 - Article
C2 - 15169841
AN - SCOPUS:3242883440
SN - 0021-9533
VL - 117
SP - 2853
EP - 2864
JO - Journal of cell science
JF - Journal of cell science
IS - 13
ER -