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| AMPK/ULK1/mTOR能量感知通路经由自噬调控BMSCs成骨分化的研究进展 |
| Research progress of AMPK/ULK1/mTOR energy sensing pathway in the regulation of osteogenic differentiation by BMSCs via autophagy |
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| DOI：10.3969/j.issn.1006-7108.2026.09.019 |
| 中文关键词: AMP活化蛋白激酶 哺乳动物雷帕霉素靶蛋白 Unc-51样激酶1 骨髓间充质干细胞 |
| 英文关键词:AMP activated protein kinase mammalian target protein of rapamycin Unc-51 like kinase 1 bone marrow mesenchymal stem cells |
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| 中文摘要: |
| 骨代谢疾病是一组涉及骨组织形成、吸收和矿化过程异常的疾病，如骨质疏松，骨关节炎等。加速成骨矿化可有效预防和治疗此类疾病，而成骨分化是成骨矿化的起始环节，因此促进成骨细胞分化是首要任务。近年来研究发现，体内多条自噬通路在不同能量状态下会影响细胞自噬，从而调节骨髓间充质干细胞（bone marrow mesenchymal stem cells，BMSCs）成骨分化。AMP活化蛋白激酶( AMP-activated protein kinase，AMPK)一方面磷酸化Unc-51样激酶1（Unc-51-like kinase 1，ULK1）的多个位点促进自噬，同时也可磷酸化结节性硬化2（tuberous sclerosis 2，TSC2）和雷帕霉素靶蛋白调节相关蛋白（regulatory associated protein of mTOR，Raptor）抑制哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）的活性进而加速自噬，三条自噬轴还会参与其他信号通路间接调节自噬，进而影响BMSCs成骨分化。本文就AMPK-ULK1、AMPK-mTOR、ULK1-mTOR自噬轴在BMSCs成骨分化过程中的研究及机制作一综述，旨在为骨质疏松、骨关节炎等骨代谢疾病的治疗提供新的靶点。 |
| 英文摘要: |
| Bone metabolic diseases are a group of abnormal conditions involving the formation, resorption, and mineralization processes of bone tissue, such as osteoporosis and osteoarthritis. Accelerating osteogenic mineralization may effectively prevent and treat such diseases. The osteogenic differentiation is the initial step of osteogenic mineralization. Therefore, promoting osteoblast differentiation is of primary importance. Recent studies have found that multiple autophagy pathways in the body affect cell autophagy under different energy states, thereby regulating bone marrow mesenchymal stem cells (BMSCs). AMP-activated protein kinase (AMPK) may phosphorylate multiple sites of Unc-51-like kinase 1 (ULK1) to promote autophagy, and it may also phosphorylate TSC2 and Raptor to inhibit the activity of mammalian target of rapamycin (mTOR), thereby accelerating autophagy. The three autophagy axes also participate in other signaling pathways to indirectly regulate autophagy, which in turn affect osteogenic differentiation of BMSCs. This article provides a review of the research and mechanisms of the AMPK-ULK1, AMPK-mTOR, and ULK1-mTOR autophagy axes in the osteogenic differentiation process of BMSCs, aiming to provide new targets for the treatment of bone metabolic diseases such as osteoporosis and osteoarthritis. |
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