成骨细胞自噬在运动改善骨质疏松的作用及机制  

Role and mechanism of osteoblast autophagy in exercise-related improvements in osteoporosis

作　　者：易小艳 曾炘瑜 刘宇威 杨雨欣 钟程浩 胡健博 陈祥和[1] YI Xiaoyan;ZENG Xinyu;LIU Yuwei;YANG Yuxin;ZHONG Chenghao;HU Jianbo;CHEN Xianghe(College of Physical Education,Yangzhou University,Yangzhou 225127,China)

机构地区：[1]扬州大学体育学院,江苏扬州225127

出　　处：《中国比较医学杂志》2025年第3期156-169,共14页Chinese Journal of Comparative Medicine

基　　金：江苏省研究生科研与实践创新计划项目(SJCX24_2206)。

摘　　要：成骨细胞(osteoblasts, OB)自噬调控骨代谢是当前生物医学领域的研究热点。OB自噬可通过介导含RUN结构域和富含半胱氨酸结构域的Beclin-1相互作用蛋白(run and cysteine rich domain containing Beclin-1 interacting protein, RUBCN)、沉默信息调节因子2相关酶1(silent information regulator of transcription 1,SIRT1)和骨保护素(osteoprotegerin, OPG)等因子来调控由衰老、氧化应激、雌激素缺乏以及糖皮质激素(glucocorticoids, GCs)所诱发的骨质疏松症(osteoporosis, OP)。OB自噬亦可通过激活Notch受体蛋白和叉头框蛋白O亚家族(forkhead box protein O subfamily, FoxO),上调成骨转录因子(如Runx2和Osterix)的表达并介导腺苷酸活化蛋白激酶(amp-activated protein kinase, AMPK)、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin complex, mTOR)、Wnt以及c-Jun氨基末端激酶(c-Jun N terminal kinase, JNK)等途径作用于OB和破骨细胞(osteoclast, OC)分化,进而调节OP。运动是改善OP的重要手段,其分子机制与上调磷脂酰肌醇3激酶(phosphatidylinositol 3 kinase, PI3K)、腺苷一磷酸(adenosine monophosphate, AMP)、肿瘤坏死因子-α(tumor necrosis factor-alpha, TNF-α)和SIRT1的表达密切相关。这些因子可激活关键因子或通路(包括AMPK、mTOR、Wnt、PI3K/丝氨酸/苏氨酸蛋白激酶B(protein kinase B, Akt)/mTOR和核因子-κB(nuclear transcription factor-κB, NF-κB)),调控下游靶基因(β-catenin、mTOR、FoxO3a和B淋巴细胞瘤-2(B cell lymphoma-2,Bcl-2))基因表达来上调自噬因子(Beclin-1、自噬相关基因(autophagy related genes,ATG)和微管相关蛋白1轻链3(microtubule-associated protein 1 light chain 3, LC3))表达,促进OB自噬以恢复体内动态平衡,进而调节骨形成和骨吸收,改善OP。然而,运动、OB自噬和OP之间的关系仍不明确,目前缺乏系统性综述。因此,我们对OB自噬在运动改善OP中的作用机制进行综述和分析,为OP的防治提供新的理论基础和研究思路。The role of osteoblast(OB) autophagy in regulating bone metabolism is a research hotspot in the field of biomedicine. OB autophagy can regulate osteoporosis(OP) induced by aging, oxidative stress, estrogen deficiency, and glucocorticoids(GCs) by mediating factors such as run and cysteine rich domain containing Beclin-1 interacting protein(RUBCN), silent information regulator of transcription 1(SIRT1), and osteoprotegerin(OPG). OB autophagy can also regulate OP by activating notch receptor(Notch) and forkhead box protein O subfamily(FoxO), up-regulating the expression of osteogenic transcription factors(such as Runx2 and Osterix), and mediating the amp-activated protein kinase(AMPK), mammalian target of rapamycin complex(mTOR), Wnt, and c-Jun n terminal kinase(JNK) pathways to act on OB and osteoclast(OC) differentiation. Exercise is an important means of improving OP, and its molecular mechanism is closely related to the up-regulation of phosphatidylinositol 3 kinase(PI3K), adenosine monophosphate(AMP), tumor necrosis factor-alpha(TNF-α), and SIRT1 expression. These in turn activate key factors or pathways(including AMPK, mTOR, Wnt, PI3K/protein kinase B(Akt)/mTOR, and nuclear transcription factor-κB(NF-κB)), regulate the expression of downstream target genes(β-catenin, mTOR, FoxO3a and B cell lymphoma-2(Bcl-2)) to up-regulate the expression of autophagy factors(Beclin-1, autophagy related genes(ATG), and microtubule-associated protein 1 light chain 3(LC3)), and promote OB autophagy to restore the dynamic balance in the body, thereby regulating bone formation and bone resorption and improving OP. The relationships among exercise, OB autophagy and OP, however, remain unclear and there is currently a lack of systematic reviews. Here we review and analyze the mechanism of OB autophagy in relation to exercise-induced improvements in OP, and provide a new theoretical basis and research ideas for the prevention and treatment of OP.

关 键 词：成骨细胞自噬 运动 骨质疏松 骨形成 骨吸收 

分 类 号：R-33[医药卫生]