| 自噬在破骨细胞中的调控作用及机制 |
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Received:July 14, 2021
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| 作者 | Author | 单位 | Unit | E-Mail |
| 缪建森 |
MIAO Jian-sen |
温州医科大学附属第二医院脊柱外科, 浙江 温州 325000 |
Department of Spinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China |
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| 王向阳 |
WANG Xiang-yang |
温州医科大学附属第二医院脊柱外科, 浙江 温州 325000 |
Department of Spinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China |
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| 金海明 |
JIN Hai-ming |
温州医科大学附属第二医院脊柱外科, 浙江 温州 325000 |
Department of Spinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China |
kkjinhaiming@126.com |
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| 期刊信息：《中国骨伤》2023年36卷，第4期，第357-363页 |
| DOI：10.12200/j.issn.1003-0034.2023.04.012 |
| 基金项目:国家自然科学基金(编号:82202757)；浙江省自然科学(编号:LQ21H060010) |
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| 破骨细胞(osteoclast,OC)是由单核巨噬细胞增殖分化而来的一类具有骨吸收功能的多核细胞,其生成过多及异常活化可诱发如骨质疏松、骨关节炎等多种骨代谢性疾病。自噬作为真核细胞中高度保守的分解代谢过程,在维持细胞稳态、应激损伤修复以及增殖分化中发挥着重要作用。近年来研究发现,自噬同样参与调控OC的生成和骨吸收功能。一方面,自噬在OC中可被多种因素诱导激活,如营养不足、低氧、核因子κB受体活化因子配体(receptor activator of nuclear factor-κB ligand,RANKL)、炎症因素、磨损颗粒、微重力环境等等,不同诱导因素如RANKL、炎症因素和磨损颗粒之间可相互联系,共同发挥作用;另一方面,激活后的自噬参与调节OC分化成熟的各个阶段,自噬可促进OC的增殖并抑制凋亡、促进OC的分化、迁移和骨吸收功能。由哺乳动物雷帕霉素靶蛋白复合物1(mammalian target of rapamycin complex 1,mTORC1)介导的经典自噬信号通路是目前研究的热点,其上游可被磷脂酰肌醇3激酶(phosphatidylinositol 3 kinase,PI-3K)/蛋白激酶B (protein kinase B,PKB),腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)等多种蛋白调控,然而,研究表明mTORC1介导的自噬可能对OC的分化和功能发挥双向调控作用,其内在机制有待进一步研究。整合素αvβ3和Rab蛋白家族分别是自噬在OC迁移和骨吸收功能中发挥作用的重要靶点。鉴于OC在各种骨疾病发生中的重要作用,阐明自噬对OC的作用及其机制对于各种骨疾病的治疗具有重要意义,自噬途径可作为一种新的治疗靶点用于临床骨疾病如骨质疏松症的治疗。 |
| [关键词]:破骨细胞 自噬 综述文献 |
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| Regulatory function and mechanism of autophagy on osteoclast |
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| Abstract:Osteoclast (OC) is multinucleated,bone-resorbing cells originated from monocyte/macrophage lineage of cells,excessive production and abnormal activation of which could lead to many bone metabolic diseases,such as osteoporosis,osteoarthritis,etc. Autophagy,as a highly conserved catabolic process in eukaryotic cells,which plays an important role in maintaining cell homeostasis,stress damage repair,proliferation and differentiation. Recent studies have found that autophagy was also involved in the regulation of osteoclast generation and bone resorption. On the one hand,autophagy could be induced and activated by various factors in osteocalsts,such as nutrient deficiency,hypoxia,receptor activator of nuclear factor(NF)-κB ligand(RANKL),inflammatory factors,wear particles,microgravity environment,etc,different inducible factors,such as RANKL,inflammatory factors,wear particles,could interact with each other and work together. On the other hand,activated autophagy is involved in regulating various stages of osteoclast differentiation and maturation,autophagy could promote proliferation of osteoclasts,inhibiting apoptosis,and promoting differentiation,migration and bone resorption of osteoclast. The classical autophagy signaling pathway mediated by mammalian target of rapamycin complex 1(mTORC1) is currently a focus of research,and it could be regulated by upstream signalings such as phosphatidylinositol 3 kinase(PI-3K)/protein kinase B (PKB),AMP-activated protein kinase(AMPK). However,the paper found that mTORC1-mediated autophagy may play a bidirectional role in regulating differentiation and function of osteoclasts,and its underlying mechanism needs to be further ciarified. Integrin αvβ3 and Rab protein families are important targets for autophagy to play a role in osteoclast migration and bone resorption,respectively. In view of important role of osteoclast in the occurrence of various bone diseases,it is of great significance to elucidate the role of autophagy on osteoclast and its mechanism for the treatment of various bone diseases. The autophagy pathway could be used as a new therapeutic target for the treatment of clinical bone diseases such as osteoporosis. |
| KEYWORDS:Osteoclasts Autophagy Review literature |
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| 引用本文，请按以下格式著录参考文献： |
| 中文格式: | 缪建森,王向阳,金海明.自噬在破骨细胞中的调控作用及机制[J].中国骨伤,2023,36(4):357~363 |
| 英文格式: | MIAO Jian-sen,WANG Xiang-yang,JIN Hai-ming.Regulatory function and mechanism of autophagy on osteoclast[J].zhongguo gu shang / China J Orthop Trauma ,2023,36(4):357~363 |
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