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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.

Sec. Bacteria and Host

Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1629805

Molecular Mechanisms Related to Bone Damage in Spinal Tuberculosis Revealed by 4D-Label Free Proteomics Analysis

Provisionally accepted
Wenxuan  XiaoWenxuan Xiao1Guangling  YangGuangling Yang2Shuqin  XuShuqin Xu1Shu  SongShu Song2Yuting  TangYuting Tang1Zhou  TianyaoZhou Tianyao2Weili  HuangWeili Huang1Lu  ZhangLu Zhang1Yutong  GuYutong Gu2*
  • 1Fudan University, Shanghai, China
  • 2Zhongshan Hospital, Fudan University, Shanghai, China

The final, formatted version of the article will be published soon.

Spinal tuberculosis (STB) is a common type of extrapulmonary tuberculosis (ETB).However, the molecular mechanism of pathological injury in STB remains unclear.The purpose of this study was to explore the pathogenic mechanism of STB, as well as compared it with Escherichia coli (E.coli) bone infection and lumbar degenerative disease (LDD) patients.In this study, the infected lumbar spine bone tissue of STB patients were collected as the infection group, LDD patients and E.coli lumbar spine infection (SEcoli) patients as the non-M.tb infection group. The protein from the bone tissue were extracted for 4D-Label Free Proteomics (4D-LFQ) analysis to compare the pathogenesis and immune mechanism of STB and SEcoli.The osteoclast growth inhibitory factor, tumor necrosis factor receptor superfamily member 11B (TNFRSF11B) and semaphorin-3A (Sema3A) were significantly downregulated in STB, while the protein Wnt-5a (WNT5A) secreted by osteoblasts was significantly up-regulated. This change in STB bone metabolism might lead to an increase in the number of osteoclasts and bone injury. In addition, the significantly upregulated expression of thymocyte selection-related family member 2 (THEMIS2) suggested THEMIS2 might be a potential therapeutic target for STB, which could control the Toll-like receptor response of macrophages. Meanwhile, PI3K-Atk antiapoptotic pathway and ECM-receptor interaction pathway were inhibited in the process of both infections.

Keywords: spinal tuberculosis, Escherichia coli infection, 4D-Label Free Proteomics, bone metabolism, molecular mechanism, Bone damage

Received: 19 May 2025; Accepted: 28 Jul 2025.

Copyright: © 2025 Xiao, Yang, Xu, Song, Tang, Tianyao, Huang, Zhang and Gu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Yutong Gu, Zhongshan Hospital, Fudan University, Shanghai, China

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