IL-17A促进慢性痛风性关节炎中破骨细胞形成

doi:10.16352/j.issn.1001-6325.2025.12.1608

基础医学与临床 ›› 2025, Vol. 45 ›› Issue (12): 1608-1613.doi: 10.16352/j.issn.1001-6325.2025.12.1608

IL-17A促进慢性痛风性关节炎中破骨细胞形成

王一博, 狄虹, 张小涵, 张昀^*, 曾学军^*

中国医学科学院北京协和医学院北京协和医院全科医学科(普通内科),北京 100730

收稿日期:2025-07-25 修回日期:2025-09-15 出版日期:2025-12-05 发布日期:2025-11-25
通讯作者: ^*zhangyun10806@pumch.cn; zxjpumch@126.com
基金资助:
协和人才培育支持计划C类项目(UBJ10806);中央高水平医院临床科研专项(2022-PUMCH-B-044)

Interleukin-17A promotes osteoclastogenesis in chronic gouty arthritis

WANG Yibo, DI Hong, ZHANG Xiaohan, ZHANG Yun^*, ZENG Xuejun^*

Department of General Internal Medicine, Peking Union Medical College Hospital, PUMC & CAMS, Beijing 100730, China

Received:2025-07-25 Revised:2025-09-15 Online:2025-12-05 Published:2025-11-25
Contact: ^*zhangyun10806@pumch.cn; zxjpumch@126.com

摘要/Abstract

摘要： 目的慢性痛风性关节炎(CGA)患者存在严重骨破坏而导致关节畸形使得预后及生活质量不佳。CGA骨破坏主要由破骨细胞介导,课题组前期发现痛风关节局部IL-17A水平升高。本研究试图探究白细胞介素17A(IL-17A)对CGA患者骨破坏的影响及可能的作用机制。方法以健康对照和CGA患者外周血单个核细胞(PBMC)在体外诱导的破骨细胞为研究对象,CGA患者来源破骨细胞分为未处理组、IL-17A处理组、线粒体自噬激动剂羰基氰化物间氯苯腙(CCCP)处理组和线粒体分裂抑制剂1(Mdivi-1)处理组。采用抗酒石酸酸性磷酸酶染色法观察并比较健康对照和未处理组破骨细胞形成情况,利用Western blot检测线粒体自噬水平及破骨细胞关键分化因子的表达。结果与健康对照相比,CGA患者PBMC形成的破骨细胞数量更多(P＜0.01)。与未处理组相比,IL-17A组破骨细胞关键转录因子表达上调,线粒体自噬水平下降(P＜0.05)。10 nmol/L及15 nmol/L Mdivi-1的干预能够促进破骨细胞关键转录因子的表达(P＜0.01)。结论 IL-17A可促进CGA患者体外破骨细胞的形成,其作用机制可能和线粒体自噬水平下降有关。

关键词: 痛风, IL-17A, 破骨细胞, 线粒体自噬, 骨破坏

Abstract: Objective Chronic gouty arthritis (CGA) can lead to severe bone erosion resulting in joint destruction, which significantly decreases the life quality and prognosis of CGA patients. Osteoclasts play an important role in this course. We aim to investigate the effect of interleukin-17A (IL-17A) on osteoclast formation in vitro in patients with chronic gouty arthritis (CGA) and its potential mechanism. Methods Osteoclasts induced in vitro from peripheral blood mononuclear cells (PBMC) of healthy controls (HC) and CGA patients were studied. CGA-derived osteoclasts were divided into four groups: untreated group, IL-17A-treated group, carbonyl cyanide 3-chlorophenylhydrazone (CCCP) group, and mitochondrial division inhibitor-1 (Mdivi-1) group. Tartrate-resistant acid phosphatase (TRAP) staining was used to observe and compare osteoclastogenesis between HC and the untreated group. Western blot was performed to detect mitophagy levels and the expression of key osteoclast differentiation factors. Results Compared with healthy controls, CGA patients showed higher osteoclastogenesis(P＜0.01). Compared with the untreated group, the IL-17A-treated group showed up-regulated expression of key osteoclast transcription factors and decreased mitophagy levels (P＜0.05). Intervention with 10 nmol/L and 15 nmol/L Mdivi-1 significantly promoted the expression of key osteoclast transcription factors (P＜0.01). Conclusions IL-17A promotes osteoclast formation in vitro in CGA patients, and its mechanism may be related to decreased mitophagy levels.

Key words: gout, IL-17A, osteoclast, mitophagy, bone erosion

中图分类号:

R593.9

王一博, 狄虹, 张小涵, 张昀, 曾学军. IL-17A促进慢性痛风性关节炎中破骨细胞形成[J]. 基础医学与临床, 2025, 45(12): 1608-1613.

WANG Yibo, DI Hong, ZHANG Xiaohan, ZHANG Yun, ZENG Xuejun. Interleukin-17A promotes osteoclastogenesis in chronic gouty arthritis[J]. Basic & Clinical Medicine, 2025, 45(12): 1608-1613.

参考文献 15

[1]	Zhou X, Liu K, Shi C, et al. Estimation of the spatial pattern of gout prevalence across China by wastewater-based epidemiology[J]. Sci Total Environ, 2024, 924: 171565. doi: 10.1007/s11926-014-0492-x.
[2]	Schlesinger N, Thiele RG. The pathogenesis of bone erosions in gouty arthritis[J]. Ann Rheum Dis, 2010, 69: 1907-1912.
[3]	McQueen FM, Chhana A, Dalbeth N. Mechanisms of joint damage in gout: evidence from cellular and imaging studies[J]. Nat Rev Rheumatol, 2012, 8: 173-181.
[4]	Miossec P. Local and systemic effects of IL-17 in joint inflammation: a historical perspective from discovery to targeting[J]. Cell Mol Immunol, 2021, 18: 860-865.
[5]	韩欣欣. 痛风性关节炎临床及发病机制研究[D]. 北京: 北京协和医学院, 2021: 38-101.
[6]	白煜佳. 痛风性关节炎患者血清及组织中Il-17水平研究[D]. 北京: 北京协和医学院, 2015: 44-60.
[7]	狄虹. IL-17参与痛风性关节炎发病机制研究及相关药物初探 [D]. 北京: 北京协和医学院, 2024: 29-60.
[8]	Chhana A, Dalbeth N. The gouty tophus: a review[J]. Curr Rheumatol Rep, 2015, 17: 19. doi: 10.1007/s11926-014-0492-x.
[9]	Yan C, Shi Y, Yuan L, et al. Mitochondrial quality control and its role in osteoporosis[J]. Front Endocrinol, 2023, 14: 1077058. doi: 10.1007/s11926-014-0492-x.
[10]	Neogi T, Jansen T L, Dalbeth N, et al. 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative[J]. Ann Rheum Dis, 2015, 74: 1789-1798.
[11]	Dalbeth N, Smith T, Nicolson B, et al. Enhanced osteoclastogenesis in patients with tophaceous gout: urate crystals promote osteoclast development through interactions with stromal cells[J]. Arthritis Rheum, 2008, 58: 1854-1865.
[12]	Tsukasaki M, Takayanagi H. Osteoimmunology: evolving concepts in bone-immune interactions in health and disease[J]. Nat Rev Immunol, 2019, 19: 626-642.
[13]	Zeng Z, Zhou X, Wang Y, et al. Mitophagy-A new target of bone disease[J]. Biomolecules, 2022, 12:1420. doi: 10.3390/biom12101420.
[14]	Jang J S, Hong S J, Mo S, et al. PINK1 restrains periodontitis-induced bone loss by preventing osteoclast mitophagy impairment[J]. Redox Biol, 2024, 69: 103023. doi: 10.1016/j.redox.2023.103023.
[15]	Liao H, Chang X, Gao L, et al. IL-17A promotes tumorigenesis and upregulates PD-L1 expression in non-small cell lung cancer[J]. J Transl Med, 2023, 21: 828. doi: 10.1186/s12967-023-04365-3.

IL-17A促进慢性痛风性关节炎中破骨细胞形成

Interleukin-17A promotes osteoclastogenesis in chronic gouty arthritis

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 15

相关文章 12

编辑推荐

Metrics

本文评价

[1]	金磊, 吴茜茜, 张晓敏, 郭洁, 王锋. 饮食治疗痛风与高尿酸血症的研究进展[J]. 基础医学与临床, 2025, 45(3): 382-389.
[2]	王一博, 韩迎东, 谢天歌, 武娟, 狄虹, 张昀, 曾学军. 24例肩部关节痛风患者的临床特点[J]. 基础医学与临床, 2025, 45(11): 1485-1490.
[3]	宁康盛, 云超, 李熠, 莫日格乐. 线粒体自噬在骨肉瘤发展和治疗中的研究进展[J]. 基础医学与临床, 2025, 45(10): 1377-1381.
[4]	张祥鑫, 李文. 线粒体自噬在肝脏缺血再灌注损伤中的作用[J]. 基础医学与临床, 2024, 44(6): 877-881.
[5]	杨丽娟, 董秋梅, 吴昊. ABCG2和SLC2A9在高尿酸血症和痛风发病中作用的研究进展[J]. 基础医学与临床, 2023, 43(9): 1467-1471.
[6]	马聪聪, 刘洋, 吕洋, 王海萍. 线粒体自噬在心肌缺血/再灌注损伤中的作用研究进展[J]. 基础医学与临床, 2023, 43(11): 1723-1727.
[7]	郑权友, 梁申菊, 舒勇, 周山, 钟渝, 盛芬, 唐铭君. C5a/C5aR1通过促γδ T细胞IL-17A表达介导IMQ诱导的小鼠银屑病样皮炎[J]. 基础医学与临床, 2022, 42(9): 1325-1332.
[8]	江罗佳, 许海波. 白藜芦醇缓解低氧/复氧诱导的TCMK1细胞线粒体自噬[J]. 基础医学与临床, 2022, 42(11): 1709-1715.
[9]	马家玲, 高艳平. miR-183靶向Bnip3l对缺氧/复氧的小鼠海马神经元细胞线粒体自噬的影响[J]. 基础医学与临床, 2021, 41(5): 698-703.
[10]	谭诗旖, 陈适. 线粒体自噬与肺部疾病的研究进展[J]. 基础医学与临床, 2020, 40(6): 842-846.
[11]	董鹏, 刘伟, 满斯亮, 李宏超, 王丽芳, 宋慧. 痛风急性发作所致发热患者临床特点分析[J]. 基础医学与临床, 2020, 40(11): 1519-1522.
[12]	于津泠李淑娟魏海萍朱弘倚韩松李俊发. 缺血性脑卒中小鼠脑和血清中IL-17A的变化及其对缺血神经元的影响[J]. 基础医学与临床, 2016, 36(4): 456-461.