Fig. 7

FZD receptors and Dkk1 coordinate RhoA/Rock activation to destabilize β-catenin in the BMMSCs from elderly mice. a-d Quantitative RT-PCR analyses for the indicated mRNA levels of BMMSCs isolated form 2- or 8-month-old mice and treated with or without rWnt3a at 100 ng/ml for 48 h. Mean ± SD, ^**p < 0.01, n = 6, Tukey-Kramer multiple comparisons test. e-g Western blotting analyses in the BMMSCs isolated form 2- or 8-month-old mice and treated with or without rWnt3a/rWnt5a at 100 ng/ml in the presence or absence of rDkk1 at 100 ng/ml for 3 h. h An integrated working model of β-catenin signaling mediated by RhoA/Rock in the regulation of aging-associated bone loss. In the BMMSCs from young subjects, APC/Axin/Gsk3β signaling mediated by FZD1, FZD4, and FZD7 overwhelms the RhoA/Rock/Jak/Gsk3β signaling mediated by FZD3, FZD6, and FZD8 to stabilize β-catenin and, in turn, enhance bone formation. However, in the BMMSCs from elderly subjects, the activation of RhoA/Rock/Jak/Gsk3β signaling mediated by FZD3, FZD6, and FZD8, in combination with the inactivation of APC/Axin/Gsk3β signaling mediated by Dkk1, Sost, and FZD1, FZD4, and FZD7 results in the destabilization of β-catenin and the subsequent attenuation of bone formation