期刊
CELL REPORTS
卷 15, 期 1, 页码 27-35出版社
CELL PRESS
DOI: 10.1016/j.celrep.2016.03.003
关键词
-
类别
资金
- Honjo International Scholarship
- Mandl fellowship
- NIH T32 training grant from the National Institute of General Medical Science
- [RO1DK104727-A1]
- [PO1AG032959-06A1]
The E3 ubiquitin ligase Smurf1 targets the master regulator of osteoblast differentiation, Runx2, for degradation, yet the function of Smurf1, if any, during osteoblast differentiation in vivo is ill defined. Here, we show that Smurf1 prevents osteoblast differentiation by decreasing Runx2 accumulation in osteoblasts. Remarkably, mice harboring a substitution mutation at serine 148 (S148) in Smurf1 that prevents its phosphorylation by AMPK (Smurf1(ki/ki)) display a premature osteoblast differentiation phenotype that is equally severe as that of Smurf1(-/-) mice, as well as a high bone mass, and are also hyperinsulinemic and hypoglycemic. Consistent with the fact that Smurf1 targets the insulin receptor for degradation, there is, in Smurf1(ki/ki) mice, an increase in insulin signaling in osteoblasts that triggers a rise in the circulating levels of osteocalcin, a hormone that favors insulin secretion. These results identify Smurf1 as a determinant of osteoblast differentiation during the development of bone formation and glucose homeostasis post-natally and demonstrate the necessity of S148 for these functions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据