FoxO3 在骨骼老化过程中调控小鼠骨间充质干细胞的命运和骨脂肪平衡。

IF 2.5 3区医学 Q3 CELL & TISSUE ENGINEERING

Stem cells and development Pub Date : 2024-04-25 DOI:10.1089/scd.2024.0055

Wei Yu, Min-Ji Tong, Guo-Hao Wu, Tian-Le Ma, Chuan-Dong Cai, Li-Peng Wang, Ying-Kai Zhang, Jin-Lun Gu, Zuoqin Yan

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引用次数: 0

摘要

与年龄有关的骨质疏松症的特点是骨间充质干细胞（BMSCs）的成骨和成脂分化失衡。叉头盒O 3（FoxO3）转录因子参与生命周期和细胞分化。本研究探讨了FoxO3是否调控与年龄相关的骨质流失和骨髓脂肪堆积。我们在体内和体外检测了衰老过程中 BMSCs 中 FoxO3 的表达水平。为了探索 FoxO3 在成骨和成脂分化过程中的作用，研究人员从年轻小鼠和老龄小鼠体内分离了原始 BMSCs。通过腺病毒载体转染调节 FoxO3 的表达。通过茜素红 S 染色、油红 O 染色、定量反转录-PCR（qRT-PCR）、Western 印迹（WB）和组织学分析评估了 FoxO3 在骨脂肪平衡中的作用。与年龄相关的骨质流失和脂肪沉积与 FoxO3 的下调有关。过表达 FoxO3 可减轻老年小鼠与年龄相关的骨质流失和骨髓脂肪堆积。从机理上讲，FoxO3分别通过下调PPAR-γ和Notch信号来减少脂肪生成和增强BMSCs的骨生成。总之，FoxO3是控制BMSCs命运的重要因子，是预防老年性骨质疏松症的潜在靶点。

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FoxO3 regulates mouse bone mesenchymal stem cell fate and bone-fat balance during skeletal aging.

Age-related osteoporosis is characterized by an imbalance between osteogenic and adipogenic differentiation in bone mesenchymal stem cells (BMSCs). Forkhead box O 3 (FoxO3) transcription factors is involved in lifespan and cell differentiation. In this study, we explore whether FoxO3 regulates age-related bone loss and marrow fat accumulation. The expression levels of FoxO3 in BMSCs during aging were detected in vivo and in vitro. To explore the role of FoxO3 in osteogenic and adipogenic differentiation, primary BMSCs were isolated from young and aged mice. FoxO3 expression was modulated by adenoviral vector transfection. The role of FoxO3 in bone-fat balance was evaluated by alizarin red S staining, oil red O staining, quantitative reverse transcription-PCR (qRT-PCR), western blot (WB) and histological analysis. Age-related bone loss and fat deposit are associated with downregulation of FoxO3. Overexpression of FoxO3 alleviated age-related bone loss and marrow fat accumulation in aged mice. Mechanistically, FoxO3 reduced adipogenesis and enhanced osteogenesis of BMSCs via downregulation of PPAR-γ and Notch signaling respectively. In conclusion, FoxO3 is an essential factor controlling the fate of BMSCs, and is a potential target for prevention of age-related osteoporosis.

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来源期刊

Stem cells and development 医学-细胞与组织工程

CiteScore

7.80

自引率

2.50%

发文量

审稿时长

3 months

期刊介绍： Stem Cells and Development is globally recognized as the trusted source for critical, even controversial coverage of emerging hypotheses and novel findings. With a focus on stem cells of all tissue types and their potential therapeutic applications, the Journal provides clinical, basic, and translational scientists with cutting-edge research and findings. Stem Cells and Development coverage includes: Embryogenesis and adult counterparts of this process Physical processes linking stem cells, primary cell function, and structural development Hypotheses exploring the relationship between genotype and phenotype Development of vasculature, CNS, and other germ layer development and defects Pluripotentiality of embryonic and somatic stem cells The role of genetic and epigenetic factors in development