Man YN, Zhong LY, Wen YL, He ML. Machine learning identifies complement factor I as a shared mediator of periodontitis and ossification of posterior longitudinal ligament. World J Orthop 2026; 17(3): 115770 [DOI: 10.5312/wjo.v17.i3.115770]
Corresponding Author of This Article
Mao-Lin He, PhD, Division of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. hemaolin@stu.gxmu.edu.cn
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Orthopedics
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Meta-Analysis
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Mar 18, 2026 (publication date) through Mar 18, 2026
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World Journal of Orthopedics
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2218-5836
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Man YN, Zhong LY, Wen YL, He ML. Machine learning identifies complement factor I as a shared mediator of periodontitis and ossification of posterior longitudinal ligament. World J Orthop 2026; 17(3): 115770 [DOI: 10.5312/wjo.v17.i3.115770]
World J Orthop. Mar 18, 2026; 17(3): 115770 Published online Mar 18, 2026. doi: 10.5312/wjo.v17.i3.115770
Machine learning identifies complement factor I as a shared mediator of periodontitis and ossification of posterior longitudinal ligament
Yu-Nan Man, Lu-Yang Zhong, Yue-Liang Wen, Mao-Lin He
Yu-Nan Man, Lu-Yang Zhong, Yue-Liang Wen, Mao-Lin He, Division of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Co-first authors: Yu-Nan Man and Lu-Yang Zhong.
Author contributions: Man YN and Zhong LY contributed equally to this work; Man YN, Zhong LY, and Wen YL designed the research study; Man YN, Zhong LY, and Wen YL performed the research and analyzed the data; He ML contributed to funding acquisition and supervision; Man YN wrote the manuscript; all authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 82160536.
Conflict-of-interest statement: All authors declare no competing interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Mao-Lin He, PhD, Division of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. hemaolin@stu.gxmu.edu.cn
Received: October 27, 2025 Revised: November 29, 2025 Accepted: December 25, 2025 Published online: March 18, 2026 Processing time: 142 Days and 20.9 Hours
Abstract
BACKGROUND
The clinical co-occurrence of periodontitis and ossification of the posterior longitudinal ligament (OPLL) suggests shared pathophysiological mechanisms, which remain poorly understood.
AIM
To elucidate the key molecular and cellular mechanisms between periodontitis and OPLL.
METHODS
Transcriptomic datasets for human periodontitis and OPLL were integrated. We performed differential gene expression analysis, weighted gene co-expression network analysis, and cross-dataset meta-analysis. A comprehensive machine learning framework incorporating 10 algorithms was applied to identify core genes, with model interpretability assessed via SHapley Additive exPlanations. Single-cell RNA sequencing data from periodontitis tissues were used to validate cell-type-specific expression, and functional enrichment analyses were conducted to elucidate relevant pathways.
RESULTS
Multi-step analysis identified complement factor I (CFI) as a principal contributor to both conditions. CFI expression was consistently upregulated and demonstrated strong discriminatory capacity for periodontitis. At single-cell resolution, endothelial cells within the periodontitis microenvironment were observed to express CFI. Functional enrichment analysis indicated that CFI-positive cells were involved in pathways related to cell adhesion (focal adhesion, adherens junctions), inflammatory signaling (PI3K-Akt pathway), and bacterial infection responses.
CONCLUSION
CFI was identified as a pivotal node connecting periodontitis and OPLL, revealing novel mechanisms and suggesting its potential as a biomarker and therapeutic target.
Core Tip: By integrating transcriptomics with machine learning across two distinct conditions, we identified complement factor I (CFI) as a candidate molecular mediator linking periodontitis and ossification of the posterior longitudinal ligament. This study provides the first computational evidence implicating a potential immune-endothelial axis, mediated by CFI, in the shared pathophysiology of these conditions.
