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Tsc1 Regulates the Balance Between Osteoblast and Adipocyte Differentiation Through Autophagy/Notch1/β‐Catenin Cascade
Author(s) -
Choi Han Kyoung,
Yuan Hebao,
Fang Fang,
Wei Xiaoxi,
Liu Lu,
Li Qing,
Guan JunLin,
Liu Fei
Publication year - 2018
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3530
Subject(s) - osteoblast , wnt signaling pathway , adipogenesis , endocrinology , medicine , chemistry , catenin , downregulation and upregulation , tsc1 , autophagy , bone marrow , adipocyte , microbiology and biotechnology , beta catenin , mesenchymal stem cell , pi3k/akt/mtor pathway , biology , signal transduction , in vitro , adipose tissue , biochemistry , apoptosis , gene
A reduction in trabecular bone mass is often associated with an increase in marrow fat in osteoporotic bones. The molecular mechanisms underlying this inverse correlation are incompletely understood. Here, we report that mice lacking tuberous sclerosis 1 ( Tsc1 ) in Osterix‐expressing cells had a significant decrease in trabecular bone mass characterized by decreased osteoblastogenesis, increased osteoclastogenesis, and increased bone marrow adiposity in vivo. In vitro study showed that Tsc1 ‐deficient bone marrow stromal cells (BMSCs) had decreased proliferation, decreased osteogenic differentiation, and increased adipogenic differentiation in association with the downregulation of Wnt/β‐catenin signaling. Mechanistically, TSC1 deficiency led to autophagy suppression and consequent Notch1 protein increase, which mediated the GSK3β‐independent β‐catenin degradation. Together, our results indicate that Tsc1 controls the balance between osteoblast and adipocyte differentiation of BMSCs. © 2018 American Society for Bone and Mineral Research.