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Peer-reviewedCC BYFrontiers in cellular and infection microbiology

A RIPK2-associated macrophage program links mycobacterial sensing to osteoclastogenesis in bone tuberculosis.

  • Yuyang Zhang1
  • Ziyang Zhang1
  • Dongyang Zhang1
  • Jiulin Tan1
  • Zhaoxin Ma1
  • Qingyang Xiao2
  • Jie Zhang1
  • Qixiu Yu1
  • Zehua Zhang1
  • Yong Tang1,3
  • Ce Dou1
  • Fei Luo1
  1. 1Department of Orthopedics, Southwest Hospital, Army Medical University, Chongqing, China.
  2. 2School of Medical and Information Engineering, Gannan Medical University, Ganzhou, Jiangxi, China.
  3. 3Department of Orthopaedics, 72nd Group Army Hospital, Huzhou Normal University, Huzhou, Zhejiang, China.
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Abstract

Introduction

In bone tuberculosis, Mycobacterium tuberculosis (Mtb) infection triggers inflammatory bone destruction, but the macrophage programs that convert Mtb signals into osteoclastogenesis remain poorly defined.Methods

We generated single-cell RNA-seq data from human spinal tuberculosis lesions and integrated them with public H3K27ac ChIP-seq, RNA-seq, Hi-C, and motif data. Key findings were validated in primary macrophages stimulated with Mtb lysate.Results

We identified 64 Mtb-induced super-enhancers, and integrated analysis prioritized RIPK2 as a candidate. Lesion-associated myeloid populations showed enhanced inflammatory and osteoclast-priming signatures, followed a mononuclear phagocyte-to-osteoclast trajectory, and exhibited a linear correlation between RIPK2 expression and osteoclast score. In mice, RIPK2 localized to CTSK-positive bone interfaces. In vitro, Mtb stimulation induced Il1b, Nfkbiz, and Tnfrsf11a expression, IL-1β secretion, and surface RANK upregulation; these responses were suppressed by the RIPK2 inhibitor GSK583.Discussion

These findings link RIPK2 to both macrophage inflammatory signaling and osteoclastogenesis in bone tuberculosis, suggesting that RIPK2 may be a target for limiting infection-driven bone destruction.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026ripk2associated,
  title = {{A RIPK2-associated macrophage program links mycobacterial sensing to osteoclastogenesis in bone tuberculosis.}},
  author = {Yuyang Zhang and Ziyang Zhang and Dongyang Zhang and Jiulin Tan and Zhaoxin Ma and Qingyang Xiao and Jie Zhang and Qixiu Yu and Zehua Zhang and Yong Tang and Ce Dou and Fei Luo},
  journal = {Frontiers in cellular and infection microbiology},
  year = {2026},
  month = oct,
  doi = {10.3389/fcimb.2026.1970405},
  url = {https://europepmc.org/article/MED/42922958},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - A RIPK2-associated macrophage program links mycobacterial sensing to osteoclastogenesis in bone tuberculosis.
AU  - Yuyang Zhang
AU  - Ziyang Zhang
AU  - Dongyang Zhang
AU  - Jiulin Tan
AU  - Zhaoxin Ma
AU  - Qingyang Xiao
AU  - Jie Zhang
AU  - Qixiu Yu
AU  - Zehua Zhang
AU  - Yong Tang
AU  - Ce Dou
AU  - Fei Luo
PY  - 2026
DA  - 2026/10/08
JO  - Frontiers in cellular and infection microbiology
DO  - 10.3389/fcimb.2026.1970405
UR  - https://europepmc.org/article/MED/42922958
AB  - Introduction  In bone tuberculosis, Mycobacterium tuberculosis (Mtb) infection triggers inflammatory bone destruction, but the macrophage programs that convert Mtb signals into osteoclastogenesis remain poorly defined.Methods  We generated single-cell RNA-seq data from human spinal tuberculosis lesions and integrated them with public H3K27ac ChIP-seq, RNA-seq, Hi-C, and motif data. Key findings were validated in primary macrophages stimulated with Mtb lysate.Results  We identified 64 Mtb-induced super-enhancers, and integrated analysis prioritized RIPK2 as a candidate. Lesion-associated myeloid populations showed enhanced inflammatory and osteoclast-priming signatures, followed a mononuclear phagocyte-to-osteoclast trajectory, and exhibited a linear correlation between RIPK2 expression and osteoclast score. In mice, RIPK2 localized to CTSK-positive bone interfaces. In vitro, Mtb stimulation induced Il1b, Nfkbiz, and Tnfrsf11a expression, IL-1β secretion, and surface RANK upregulation; these responses were suppressed by the RIPK2 inhibitor GSK583.Discussion  These findings link RIPK2 to both macrophage inflammatory signaling and osteoclastogenesis in bone tuberculosis, suggesting that RIPK2 may be a target for limiting infection-driven bone destruction.
SN  - 2235-2988
ER  -