中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (28): 7437-7446.doi: 10.12307/2026.821

• 组织工程相关大数据分析 Big data analysis in tissue engineering • 上一篇    下一篇

血浆代谢物与骨关节炎的关联性

李云鹏1，2，吕玉强2，张佳林2，汤  优2，王  恺3，赵文志1   

  1. 1大连医科大学附属第二医院，辽宁省大连市  116000；2滨州市人民医院，山东省滨州市  256600；3滨州医学院，山东省滨州市  256600
  • 收稿日期:2025-08-25 修回日期:2025-12-08 出版日期:2026-10-08 发布日期:2026-02-26
  • 通讯作者: 赵文志，教授，主任医师，博士生导师，大连医科大学附属第二医院骨科，辽宁省大连市 116000
  • 作者简介:李云鹏，男，1990年生，山东省滨州市人，汉族，大连医科大学博士在读，主治医师，主要从事骨科相关疾病的诊治与研究。
  • 基金资助:
    山东省自然科学基金项目(ZR2022QH391)，项目负责人：王恺；大连市数字骨科重点实验室项目，项目负责人：赵文志；滨州市人民医院课题(XJ2024000803)，项目负责人：李云鹏

Association between plasma metabolites and osteoarthritis

Li Yunpeng1, 2, Lyu Yuqiang2, Zhang Jialin2, Tang You2, Wang Kai3, Zhao Wenzhi1   

  1. 1Second Affiliated Hospital of Dalian Medical University, Dalian 116000, Liaoning Province, China; 2Binzhou People’s Hospital, Binzhou 256600, Shandong Province, China; 3Binzhou Medical University, Binzhou 256600, Shandong Province, China 
  • Received:2025-08-25 Revised:2025-12-08 Online:2026-10-08 Published:2026-02-26
  • Contact: Zhao Wenzhi, Professor, Chief physician, Doctoral supervisor, Second Affiliated Hospital of Dalian Medical University, Dalian 116000, Liaoning Province, China
  • About author:Li Yunpeng, Attending physician, MD candidate, Second Affiliated Hospital of Dalian Medical University, Dalian 116000, Liaoning Province, China; Binzhou People’s Hospital, Binzhou 256600, Shandong Province, China
  • Supported by:
    Shandong Provincial Natural Science Foundation Project, No. ZR2022QH391 (to WK); Dalian Key Laboratory of Digital Orthopedics Project (to ZWZ); Binzhou People’s Hospital Project, No. XJ2024000803 (to LYP)

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摘要：



文题释义：
骨关节炎：一种常见的慢性退行性关节疾病，主要表现为关节软骨的进行性破坏、关节边缘骨赘形成(骨刺)以及继发性滑膜炎症。
孟德尔随机化：一种基于遗传变异的因果推断方法，利用工具变量来评估暴露因素与结局之间的潜在因果关系。孟德尔随机化的核心思想借鉴了孟德尔遗传定律，即基因变异在人群中的随机分配，从而减少混杂因素的影响，提高因果推断的可靠性。

背景：近年来，代谢紊乱被证实与骨关节炎的发病密切相关，但血浆代谢物与骨关节炎的因果关系尚未被系统阐明。
目的：利用两样本孟德尔随机化法探究1 400种血浆代谢物与9种骨关节炎的因果关系。
方法：将1 400种血浆代谢物的全基因组关联研究作为暴露，将9种骨关节炎(任何部位骨关节炎、早期骨关节炎、膝和/或髋骨关节炎、膝骨关节炎、髋骨关节炎、脊柱骨关节炎、手指骨关节炎、手部骨关节炎、拇指骨关节炎)设为结局，将单核苷酸多态性作为工具变量，并选择敏感的单核苷酸多态性进行孟德尔随机化分析，以逆方差加权法(作为主要分析手段，同时，采用MR-Egger、加权中位数法、简单中位数法及加权众数法进行交叉验证，采用MR-PRESSO、Cochran’s Q检验等方法共同完成敏感性及多效性检验，得到的数据采用错误发现率方法进行进一步矫正。
结果与结论：孟德尔随机化分析显示，手指骨关节炎、手部骨关节炎、髋骨关节炎、脊柱骨关节炎均无符合错误发现率< 0.05的结果，任何部位骨关节炎、早期骨关节炎、膝和/或髋骨关节炎、膝骨关节炎、拇指骨关节炎均与多种代谢物具有显著的因果关系，甘氨酸、丝氨酸、高水苏碱、硫酸盐等代谢物均与多种骨关节炎关系密切；对比部分非负重关节骨关节炎(如手指骨关节炎、手部骨关节炎)，血浆代谢物与负重关节骨关节炎(如膝骨关节炎、髋骨关节炎)的敏感性更强。该研究为中国人群骨关节炎的代谢干预策略提供了理论依据，也为中国开展复杂疾病的机制研究提供了方法学范式。
https://orcid.org/0000-0003-1718-0194(李云鹏)


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 血浆代谢物, 骨关节炎, 孟德尔随机化, 工具变量, 因果关系, 发病机制

Abstract: BACKGROUND: In recent years, metabolic disorders have been confirmed to be closely related to the onset of osteoarthritis, but the causal relationship between plasma metabolites and osteoarthritis has not been systematically elucidated. 
OBJECTIVE: To explore the causal relationship between 1 400 plasma metabolites and 9 types of osteoarthritis using two-sample Mendelian randomization.
METHODS: A genome-wide association study of 1 400 metabolites was used as the exposure. Nine types of arthritis, namely any-site osteoarthritis, early osteoarthritis, knee and/or hip osteoarthritis, knee osteoarthritis, hip osteoarthritis, spinal osteoarthritis, finger osteoarthritis, hand osteoarthritis, and thumb osteoarthritis, were set as the outcomes. Single nucleotide polymorphisms were used as instrumental variables, and sensitive single nucleotide polymorphisms were selected for Mendelian randomization analysis. The inverse variance weighted method was used as the main analysis approach. Meanwhile, four methods, namely MR-Egger, weighted median, simple mode, and weighted mode, were employed for cross-validation. Sensitivity and pleiotropy tests were conducted using MR-PRESSO and Cochran’s Q test, and the obtained data were further corrected using the false discovery rate method.
RESULTS AND CONCLUSION: Mendelian randomization analysis showed that no false discovery rate (< 0.05) was found for finger osteoarthritis, hand osteoarthritis, hip osteoarthritis, or spinal osteoarthritis. Any-site osteoarthritis, early osteoarthritis, knee and/or hip osteoarthritis, knee osteoarthritis, and thumb osteoarthritis were significantly causally related to multiple metabolites. Glycine, serine, homostachydrine, and sulfate metabolites were all closely related to various types of osteoarthritis. Compared with some non-weight-bearing joint osteoarthritis (such as finger and hand osteoarthritis), plasma metabolites showed greater sensitivity to weight-bearing joint osteoarthritis (such as knee osteoarthritis and hip osteoarthritis). This study provides a theoretical basis for metabolic intervention strategies for osteoarthritis in Chinese population and a methodological paradigm for conducting mechanistic research on complex diseases in China.


Key words: plasma metabolites, osteoarthritis, Mendelian randomization, instrumental variable, causality, pathogenesis

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