| First Author | Song L | Year | 2022 |
| Journal | Bone | Volume | 156 |
| Pages | 116320 | PubMed ID | 34973494 |
| Mgi Jnum | J:319774 | Mgi Id | MGI:6865346 |
| Doi | 10.1016/j.bone.2021.116320 | Citation | Song L, et al. (2022) Postnatal deletion of beta-catenin in preosteoblasts regulates global energy metabolism through increasing bone resorption and adipose tissue fibrosis. Bone 156:116320 |
| abstractText | Many studies revealed bone can regulate global energy metabolism and our previous study also showed that Wnt/beta-catenin pathway is involved in this process. To better understand the participation of canonical Wnt pathway in energy metabolism, we examined the beta-catenin knock-out (beta-cat KO) mice by crossing the osterix-cre transgenic mice with beta-catenin(flox/flox) mice. First, we identified that postnatal deletion of beta-catenin in preosteoblasts led to decreased fat mass and increased energy expenditure in mice. Osteoprotegerin administration largely rescued the decreased fat mass and partly normalized the energy expenditure accompanied by the inhibition of bone resorption. Anti-resorption with alendronate or RANKL-antibody could also partly rescued the decreased bone mass, decreased fat mass and increased energy expenditure in beta-cat KO mice. We further found that the adipose cells in the inguinal fat tissue were smaller and the extracellular matrix components around adipocytes accumulated more in beta-cat KO mice than their controls by histomorphology. Gene analysis by RT-PCR showed that the expression of collagen VI is 4.8 folds in adipose tissue of the beta-cat KO mice compared with the control mice. We further detected the expression of cytokines which were related to fibrosis and the data showed that the level of TGF-beta1 was elevated in both of bone marrow serum and adipose tissue derived from the beta-cat KO mice. After administration of TGF-beta1 neutralizing antibody, the impaired energy metabolism was partly rescued in beta-cat KO mice. Besides, anti-resorption treatment and TGF-beta1 antibody could partly suppress the increased expression of genes related to fat tissue fibrosis. These results indicate that the abnormal global energy metabolism in beta-cat KO mice may be attributed to increasing bone resorption and adipose tissue fibrosis. |
