RAB12在骨质疏松症中抑制成骨分化和驱动代谢失调中的作用

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-03-25 DOI:10.1016/j.lfs.2025.123590

Pengfei Ji , Quanfeng Li , Yunhui Zhang , Jiahao Jin , Yibin Zhang , Zihao Yuan , Guozhen Shen , Qian Cao , Yanfeng Wu , Peng Wang , Wenjie Liu

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引用次数: 0

摘要

目的间充质干细胞（MSCs）的成骨分化在骨质疏松症中起着至关重要的作用，骨微环境的代谢水平直接影响绝经后妇女的代谢失调。RAB12是小GTPase rabb家族蛋白的一员，已知在自噬中起重要作用。然而，RAB12在骨质疏松性hMSCs成骨分化中的作用尚不清楚。材料和方法采用免疫组化染色验证RAB12在老年骨质疏松小鼠模型和卵巢切除（OVX）小鼠模型中的高表达。采用共免疫沉淀（Co-IP）和LC-MS/MS方法探索可能与RAB12相互作用的下游蛋白。将含有RAB12 siRNA序列的腺病毒注入OVX骨质疏松小鼠的尾静脉，分析RAB12/PCBP1/GLUT1轴对MSC成骨分化的影响。我们发现RAB12在老年骨质疏松患者和骨质疏松小鼠模型中表达上调。RAB12在体内和体外均负向调控hMSCs的成骨分化。RAB12与PCBP1蛋白相互作用，当其表达水平改变时影响其自噬降解。RAB12通过影响PCBP1的自噬降解来调节GLUT1的转录水平，从而影响MSC对葡萄糖摄取的调节，进而影响MSC成骨分化和代谢变化。ab12通过PCBP1/GLUT1轴负向调控成骨分化，影响骨微环境中的葡萄糖代谢水平。RAB12可能作为治疗骨质疏松症和绝经后代谢失调的潜在靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

The role of RAB12 in inhibiting osteogenic differentiation and driving metabolic dysregulation in osteoporosis

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The role of RAB12 in inhibiting osteogenic differentiation and driving metabolic dysregulation in osteoporosis

Aims

The osteogenic differentiation of mesenchymal stem cells (MSCs) is crucial in osteoporosis, and the metabolic level of the bone microenvironment directly affects metabolic dysregulation in postmenopausal women. RAB12 is a member of the small GTPase Rab family proteins, known to play an important role in autophagy. However, the role of RAB12 in the osteogenic differentiation of osteoporotic hMSCs remains unclear.

Materials and method

Immunohistochemical staining was used to validate the high expression of RAB12 in aged osteoporotic mouse models and ovariectomized (OVX) mouse models. Co-immunoprecipitation (Co-IP) and LC-MS/MS were employed to explore downstream proteins that may interact with RAB12. Adenovirus containing RAB12 siRNA sequences was injected into the tail vein of OVX osteoporotic mice to analyze the impact of the RAB12/PCBP1/GLUT1 axis on MSC osteogenic differentiation.

Key findings

We found that RAB12 expression is upregulated in elderly osteoporotic patients and in osteoporotic mouse models. RAB12 negatively regulates the osteogenic differentiation of hMSCs both in vivo and in vitro. RAB12 interacts with the PCBP1 protein, affecting its autophagic degradation when its expression levels change. RAB12 regulates the transcriptional level of GLUT1 by influencing the autophagic degradation of PCBP1, thereby affecting MSC's regulation of glucose uptake, which in turn impacts MSC osteogenic differentiation and metabolic changes.

Significance

RAB12 negatively regulates osteogenic differentiation through the PCBP1/GLUT1 axis, affecting glucose metabolism levels in the bone microenvironment. RAB12 may serve as a potential target for the treatment of osteoporosis and postmenopausal metabolic dysregulation.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

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