Dataset Information

Tsc1 Regulates the Balance Between Osteoblast and Adipocyte Differentiation Through Autophagy/Notch1/?-Catenin Cascade.

ABSTRACT: 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/?-catenin signaling. Mechanistically, TSC1 deficiency led to autophagy suppression and consequent Notch1 protein increase, which mediated the GSK3?-independent ?-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.

SUBMITTER: Choi HK

PROVIDER: S-EPMC6248888 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Tsc1 Regulates the Balance Between Osteoblast and Adipocyte Differentiation Through Autophagy/Notch1/β-Catenin Cascade.

Choi Han Kyoung HK Yuan Hebao H Fang Fang F Wei Xiaoxi X Liu Lu L Li Qing Q Guan Jun-Lin JL Liu Fei F

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20180719 11

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-defic ...[more]

PMID: 29924882

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Project description:Bone marrow mesenchymal progenitor cells are precursors for various cell types including osteoblasts, adipocytes, and chondrocytes. The external environment and signals act to direct the pathway of differentiation. Importantly, situations such as aging and chronic kidney disease display alterations in the balance of osteoblast and adipocyte differentiation, adversely affecting bone integrity. Iron deficiency, which can often occur during aging and chronic kidney disease, is associated with reduced bone density. The purpose of this study was to assess the effects of iron deficiency on the capacity of progenitor cell differentiation pathways. Mouse and human progenitor cells, differentiated under standard osteoblast and adipocyte protocols in the presence of the iron chelator deferoxamine (DFO), were used. Under osteogenic conditions, 5μM DFO significantly impaired expression of critical osteoblast genes, including osteocalcin, type 1 collagen, and dentin matrix protein 1. This led to a reduction in alkaline phosphatase activity and impaired mineralization. Despite prolonged exposure to chronic iron deficiency, cells retained viability as well as normal hypoxic responses with significant increases in transferrin receptor and protein accumulation of hypoxia inducible factor 1α. Similar concentrations of DFO were used when cells were maintained in adipogenic conditions. In contrast to osteoblast differentiation, DFO modestly suppressed adipocyte gene expression of peroxisome-proliferating activated receptor gamma, lipoprotein lipase, and adiponectin at earlier time points with normalization at later stages. Lipid accumulation was also similar in all conditions. These data suggest the critical importance of iron in osteoblast differentiation, and as long as the external stimuli are present, iron deficiency does not impede adipogenesis. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Dataset Information

Tsc1 Regulates the Balance Between Osteoblast and Adipocyte Differentiation Through Autophagy/Notch1/?-Catenin Cascade.

Publications

Tsc1 Regulates the Balance Between Osteoblast and Adipocyte Differentiation Through Autophagy/Notch1/β-Catenin Cascade.

Similar Datasets

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