
浏览全部资源
扫码关注微信
1.联勤保障部队第920医院骨科,云南 昆明 650032
2.昆明市第三人民医院肝病消化科,云南 昆明 650032
蒙旭晗,E-mail:369210354@qq.com
收稿:2025-04-17,
纸质出版:2026-03-25
移动端阅览
胡清,史冲,阮默等.cGAS-STING通路在骨与关节疾病中的研究进展[J].局解手术学杂志,2026,35(03):265-269.
HU Qing,SHI Chong,RUAN Mo,et al.Research progress of the cGAS-STING pathway in bone and joint diseases[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(03):265-269.
胡清,史冲,阮默等.cGAS-STING通路在骨与关节疾病中的研究进展[J].局解手术学杂志,2026,35(03):265-269. DOI: 10.11659/jjssx.04E025096.
HU Qing,SHI Chong,RUAN Mo,et al.Research progress of the cGAS-STING pathway in bone and joint diseases[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(03):265-269. DOI: 10.11659/jjssx.04E025096.
环磷酸鸟苷-腺苷合成酶-干扰素基因刺激因子(cGAS-STING)通路是胞质DNA介导先天免疫与炎症反应的核心信号轴,其失衡与多种骨与关节疾病密切相关。在骨肉瘤中激活该通路可增强抗肿瘤免疫,而在多种退行性及炎症性关节疾病中其持续激活可促进无菌性炎症与组织退变,因而成为重要的治疗靶点。本文对cGAS-STING通路在骨与关节疾病中的最新研究进展作一综述,以期为其临床治疗提供参考。
The cyclic guanosine-adenosine synthetase-interferon gene stimulating factor (cGAS-STING) pathway is the core signaling axis by which cytosolic DNA triggers innate immunity and inflammatory responses, and its dysregulation is closely associated with the development of various bone and joint diseases. Activation of this pathway in osteosarcoma can enhance anti-tumor immunity, whereas its persistent activation in multiple degenerative and inflammatory joint diseases can promote sterile inflammation and tissue degeneration, making it an important therapeutic target. This article reviews the latest research progress of the cGAS-STING pathway in bone and joint diseases,aiming to provide a reference for its clinical treatment.
Gulen MF , Samson N , Keller A , et al . cGAS-STING drives ageing-related inflammation and neurodegeneration [J]. Nature , 2023 , 620 ( 7973 ): 374 - 380 . doi: 10.1038/s41586-023-06373-1 http://dx.doi.org/10.1038/s41586-023-06373-1 .
Dvorkin S , Cambier S , Volkman HE , et al . New frontiers in the cGAS-STING intracellular DNA-sensing pathway [J]. Immunity , 2024 , 57 ( 4 ): 718 - 730 . doi: 10.1016/j.immuni.2024.02.019 http://dx.doi.org/10.1016/j.immuni.2024.02.019 .
Guo Q , Chen X , Chen J , et al . STING promotes senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the NF-κB signaling pathway [J]. Cell Death Dis , 2021 , 12 ( 1 ): 13 . doi: 10.1038/s41419-020-03341-9 http://dx.doi.org/10.1038/s41419-020-03341-9 .
Xu Q , Xing J , Wang S , et al . The role of the cGAS-STING pathway in metabolic diseases [J]. Heliyon , 2024 , 10 ( 12 ): e33093 . doi: 10.1016/j.heliyon.2024.e33093 http://dx.doi.org/10.1016/j.heliyon.2024.e33093 .
Sun L , Wu J , Du F , et al . Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type Ⅰ interferon pathway [J]. Science , 2013 , 339 ( 6121 ): 786 - 791 . doi: 10.1126/science.1232458 http://dx.doi.org/10.1126/science.1232458 .
Burdette DL , Monroe KM , Sotelo-Troha K , et al . STING is a direct innate immune sensor of cyclic di-GMP [J]. Nature , 2011 , 478 ( 7370 ): 515 - 518 . doi: 10.1038/nature10429 http://dx.doi.org/10.1038/nature10429 .
Chowdhury A , Witte S , Aich A . Role of mitochondrial nucleic acid sensing pathways in health and patho-physiology [J]. Front Cell Dev Biol , 2022 , 10 : 796066 . doi: 10.3389/fcell.2022.796066 http://dx.doi.org/10.3389/fcell.2022.796066 .
Dang XTT , Phung CD , Lim CMH , et al . Dendritic cell-targeted delivery of antigens using extracellular vesicles for anti-cancer immunotherapy [J]. Cell Prolif , 2024 , 57 ( 7 ): e13622 . doi: 10.1111/cpr.13622 http://dx.doi.org/10.1111/cpr.13622 .
Cho MG , Kumar RJ , Lin CC , et al . MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis [J]. Nature , 2024 , 625 ( 7995 ): 585 - 592 . doi: 10.1038/s41586-023-06889-6 http://dx.doi.org/10.1038/s41586-023-06889-6 .
Gayen S , Mukherjee S , Dasgupta S , et al . Emerging druggable targets for immune checkpoint modulation in cancer immunotherapy:the iceberg lies beneath the surface [J]. Apoptosis , 2024 , 29 ( 11/12 ): 1879 - 1913 . doi: 10.1007/s10495-024-02022-8 http://dx.doi.org/10.1007/s10495-024-02022-8 .
Shen C , Xu P , Zhang C , et al . Structure-activity relationship study of 1H-Pyrrole-3-carbonitrile derivatives as STING receptor agonists [J]. ACS Med Chem Lett , 2023 , 14 ( 8 ): 1079 - 1087 . doi: 10.1021/acsmedchemlett.3c00208 http://dx.doi.org/10.1021/acsmedchemlett.3c00208 .
Motani K , Saito-Tarashima N , Nishino K , et al . The Golgi-resident protein ACBD3 concentrates STING at ER-Golgi contact sites to drive export from the ER [J]. Cell Rep , 2022 , 41 ( 12 ): 111868 . doi: 10.1016/j.celrep.2022.111868 http://dx.doi.org/10.1016/j.celrep.2022.111868 .
Shang M , Lu K , Guan W , et al . 2',3'-cyclic GMP-AMP dinucleotides for STING-mediated immune modulation: principles, immunotherapeutic potential, and synthesis [J]. ChemMedChem , 2022 , 17 ( 2 ): e202100671 . doi: 10.1002/cmdc.202100671 http://dx.doi.org/10.1002/cmdc.202100671 .
Yu S , Yao X . Advances on immunotherapy for osteosarcoma [J]. Mol Cancer , 2024 , 23 ( 1 ): 192 . doi: 10.1186/s12943-024-02105-9 http://dx.doi.org/10.1186/s12943-024-02105-9 .
Shi T , Kang J , Wang Q , et al . Advancements in research regarding the influence of the tumor microenvironment on the proliferation and metastasis of osteosarcoma (review) [J]. Oncol Lett , 2026 , 31 ( 1 ): 20 . doi: 10.3892/ol.2025.15373 http://dx.doi.org/10.3892/ol.2025.15373 .
O'Donoghue JC , Freeman FE . Make it STING: nanotechnological approaches for activating cGAS/STING as an immunomodulatory node in osteosarcoma [J]. Front Immunol , 2024 , 15 : 1403538 . doi: 10.3389/fimmu.2024.1403538 http://dx.doi.org/10.3389/fimmu.2024.1403538 .
Menz A , Zerneke J , Viehweger F , et al . Stimulator of interferon genes protein (STING) expression in cancer cells: a tissue microarray study evaluating more than 18,000 tumors from 139 different tumor entities [J]. Cancers (Basel) , 2024 , 16 ( 13 ): 2425 . doi: 10.3390/cancers16132425 http://dx.doi.org/10.3390/cancers16132425 .
Withers SS , Moeller CE , Quick CN , et al . Effect of stimulator of interferon genes (STING) signaling on radiation-induced chemokine expression in human osteosarcoma cells [J]. PLoS One , 2023 , 18 ( 4 ): e0284645 . doi: 10.1371/journal.pone.0284645 http://dx.doi.org/10.1371/journal.pone.0284645 .
Nassour J , Aguiar LG , Correia A , et al . Telomere-to-mitochondria signalling by ZBP1 mediates replicative crisis [J]. Nature , 2023 , 614 ( 7949 ): 767 - 773 . doi: 10.1038/s41586-023-05710-8 http://dx.doi.org/10.1038/s41586-023-05710-8 .
Li C , Zhang Y , Liu J , et al . Mitochondrial DNA stress triggers autophagy-dependent ferroptotic death [J]. Autophagy , 2021 , 17 ( 4 ): 948 - 960 . doi: 10.1080/15548627.2020.1739447 http://dx.doi.org/10.1080/15548627.2020.1739447 .
Li C , Sun S , Zhuang Y , et al . CTSB nuclear translocation facilitates DNA damage and lysosomal stress to promote retinoblastoma cell death [J]. Mol Biotechnol , 2024 , 66 ( 9 ): 2583 - 2594 . doi: 10.1007/s12033-023-01042-0 http://dx.doi.org/10.1007/s12033-023-01042-0 .
Wu W , Zhang Z , Jing D , et al . SGLT2 inhibitor activates the STING/IRF3/IFN-β pathway and induces immune infiltration in osteosarcoma [J]. Cell Death Dis , 2022 , 13 ( 6 ): 523 . doi: 10.1038/s41419-022-04980-w http://dx.doi.org/10.1038/s41419-022-04980-w .
Cho YK , Jung CH . Sodium-glucose cotransporter 2 inhibitors as emerging anticancer agents [J]. Diabetes Metab J , 2026 , 50 ( 1 ): 1 - 18 . doi: 10.4093/dmj.2025.0964 http://dx.doi.org/10.4093/dmj.2025.0964 .
Eek Mariampillai A , Hauge S , Øynebråten I , et al . Caspase activation counteracts interferon signaling after G2 checkpoint abrogation by ATR inhibition in irradiated human cancer cells [J]. Front Oncol , 2022 , 12 : 981332 . doi: 10.3389/fonc.2022.981332 http://dx.doi.org/10.3389/fonc.2022.981332 .
Chen Q , Tu S , Tang D , et al . Amyloid-β peptide treatment reverses bone loss in the mandibular condyle via Wnt signalling pathway [J]. Bone Rep , 2024 , 22 : 101788 . doi: 10.1016/j.bonr.2024.101788 http://dx.doi.org/10.1016/j.bonr.2024.101788 .
Yin Z , Gong G , Wang X , et al . The dual role of autophagy in periprosthetic osteolysis [J]. Front Cell Dev Biol , 2023 , 11 : 1123753 . doi: 10.3389/fcell.2023.1123753 http://dx.doi.org/10.3389/fcell.2023.1123753 .
Chen X , He W , Sun M , et al . STING inhibition accelerates the bone healing process while enhancing type H vessel formation [J]. Faseb J , 2021 , 35 ( 11 ): e21964 . doi: 10.1096/fj.202100069RR http://dx.doi.org/10.1096/fj.202100069RR .
Gao Z , Gao Z , Zhang H , et al . Targeting STING:from antiviral immunity to treat osteoporosis [J]. Front Immunol , 2022 , 13 : 1095577 . doi: 10.3389/fimmu.2022.1095577 http://dx.doi.org/10.3389/fimmu.2022.1095577 .
Wang Z , Hu X , Cui P , et al . Progress in understanding the role of cGAS-STING pathway associated with programmed cell death in intervertebral disc degeneration [J]. Cell Death Discov , 2023 , 9 ( 1 ): 377 . doi: 10.1038/s41420-023-01607-7 http://dx.doi.org/10.1038/s41420-023-01607-7 .
Guo Q , Zhu D , Wang Y , et al . Targeting STING attenuates ROS induced intervertebral disc degeneration [J]. Osteoarthritis Cartilage , 2021 , 29 ( 8 ): 1213 - 1224 . doi: 10.1016/j.joca.2021.04.017 http://dx.doi.org/10.1016/j.joca.2021.04.017 .
Liang ZH , Song J , Shangguan WJ , et al . Melatonin mitigates matrix stiffness-induced intervertebral disk degeneration by inhibiting reactive oxygen species and melatonin receptors mediated PI3K/AKT/NF-κB pathway [J]. Am J Physiol Cell Physiol , 2024 , 327 ( 5 ): C1236 - C1248 . doi: 10.1152/ajpcell.00630.2023 http://dx.doi.org/10.1152/ajpcell.00630.2023 .
Tian Y , Bao Z , Ji Y , et al . Epigallocatechin-3-gallate protects H 2 O 2 -induced nucleus pulposus cell apoptosis and inflammation by inhibiting cGAS/Sting/NLRP3 activation [J]. Drug Des Devel Ther , 2020 , 14 : 2113 - 2122 . doi: 10.2147/dddt.S251623 http://dx.doi.org/10.2147/dddt.S251623 .
Oduro PK , Zheng X , Wei J , et al . The cGAS-STING signaling in cardiovascular and metabolic diseases: future novel target option for pharmacotherapy [J]. Acta Pharm Sin B , 2022 , 12 ( 1 ): 50 - 75 . doi: 10.1016/j.apsb.2021.05.011 http://dx.doi.org/10.1016/j.apsb.2021.05.011 .
Ren C , Jin J , Li C , et al . Metformin inactivates the cGAS-STING pathway through autophagy and suppresses senescence in nucleus pulposus cells [J]. J Cell Sci , 2022 , 135 ( 15 ): jcs259738 . doi: 10.1242/jcs.259738 http://dx.doi.org/10.1242/jcs.259738 .
Li S , Liao Z , Luo R , et al . Autophagy-based unconventional secretory for AIM2 inflammasome drives DNA damage resistance during intervertebral disc degeneration [J]. Front Cell Dev Biol , 2021 , 96 : 72847 . doi: 10.3389/fcell.2021.672847 http://dx.doi.org/10.3389/fcell.2021.672847 .
Messaoud-Nacer Y , Culerier E , Rose S , et al . STING agonist diABZI induces PANoptosis and DNA mediated acute respiratory distress syndrome (ARDS) [J]. Cell Death Dis , 2022 , 13 ( 3 ): 269 . doi: 10.1038/s41419-022-04664-5 http://dx.doi.org/10.1038/s41419-022-04664-5 .
Xiang H , Zhao W , Jiang K , et al . Progress in regulating inflammatory biomaterials for intervertebral disc regeneration [J]. Bioact Mater , 2024 , 33 : 506 - 531 . doi: 10.1016/j.bioactmat.2023.11.021 http://dx.doi.org/10.1016/j.bioactmat.2023.11.021 .
Shin Y , Cho D , Kim SK , et al . STING mediates experimental osteoarthritis and mechanical allodynia in mouse [J]. Arthritis Res Ther , 2023 , 25 ( 1 ): 90 . doi: 10.1186/s13075-023-03075-x http://dx.doi.org/10.1186/s13075-023-03075-x .
Xu D , Zhang L , Song C , et al . Acacetin targets STING to alleviate the destabilization of the medial meniscus-induced osteoarthritis in mice [J]. Naunyn Schmiedebergs Arch Pharmacol , 2024 , 397 ( 11 ): 8863 - 8878 . doi: 10.1007/s00210-024-03167-8 http://dx.doi.org/10.1007/s00210-024-03167-8 .
Yang X , Zhao L , Pang Y . cGAS-STING pathway in pathogenesis and treatment of osteoarthritis and rheumatoid arthritis [J]. Front Immunol , 2024 , 15 : 1384372 . doi: 10.3389/fimmu.2024.1384372 http://dx.doi.org/10.3389/fimmu.2024.1384372 .
Weng W , Liu Y , Hu Z , et al . Macrophage extracellular traps promote tumor-like biologic behaviors of fibroblast-like synoviocytes through cGAS-mediated PI3K/Akt signaling pathway in patients with rheumatoid arthritis [J]. J Leukoc Biol , 2024 , 115 ( 1 ): 116 - 129 . doi: 10.1093/jleuko/qiad102 http://dx.doi.org/10.1093/jleuko/qiad102 .
Tansakul M , Thim-Uam A , Saethang T , et al . Deficiency of STING promotes collagen-specific antibody production and B cell survival in collagen-induced arthritis [J]. Front Immunol , 2020 , 11 : 1101 . doi: 10.3389/fimmu.2020.01101 http://dx.doi.org/10.3389/fimmu.2020.01101 .
Ding Q , Hu W , Wang R , et al . Signaling pathways in rheumatoid arthritis:implications for targeted therapy [J]. Signal Transduct Target Ther , 2023 , 8 ( 1 ): 68 . doi: 10.1038/s41392-023-01331-9 http://dx.doi.org/10.1038/s41392-023-01331-9 .
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621