Damage-Associated Molecular Patterns and Trained Immunity of Monocyte-Macrophage Populations in Osteoarthritis: Potential Molecular Links and Therapeutic Opportunities.
- 1The First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China.
- 2College of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming 650500, China.
Abstract
Osteoarthritis (OA) is now widely discussed as a whole-joint immunometabolic disease involving cartilage, synovium, and subchondral bone, rather than as cartilage degeneration driven only by mechanical stress. Tissue injury, cell death, mitochondrial dysfunction, and extracellular matrix degradation can lead to the persistent release of damage-associated molecular patterns (DAMPs), which activate innate immune responses through pattern recognition receptors (PRRs). A key unresolved issue is why inflammation can persist or recur when there is no continuous external stimulus. Trained immunity provides an emerging framework for approaching this problem, with initial direct evidence now available in circulating monocytes from knee OA but broader validation still lacking. Following an initial stimulus and a subsequent resting interval, monocytes and macrophages may retain epigenetic and metabolic alterations that modify their responses to later homologous or heterologous challenges. This review summarizes the sources of DAMPs and their recognition mechanisms in the OA microenvironment, with particular attention to their potential links with trained immunity in monocyte-macrophage populations. We discuss PRR-mediated changes in chromatin accessibility, histone modifications, DNA methylation, and non-coding RNA regulation, as well as immunometabolic events such as enhanced glycolysis, tricarboxylic acid cycle remodeling, mitochondrial dysfunction, and accumulation of key metabolites. We also examine how monocyte-macrophage populations with persistent hyperresponsiveness after stimulus withdrawal and restimulation may contribute to persistent synovitis, cartilage matrix degradation, and abnormal subchondral bone remodeling. Finally, we summarize therapeutic opportunities potentially relevant to the proposed links between DAMP signaling and trained immunity. Recent evidence that high-mobility group box 1 (HMGB1) primes a trained phenotype in circulating monocytes provides initial direct support for DAMP-associated trained immunity in knee OA. However, its generalizability across independent cohorts, other DAMP classes, myeloid-cell compartments, disease stages, and OA phenotypes remains to be established.
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BibTeX
@article{zhang2026damageassociated,
title = {{Damage-Associated Molecular Patterns and Trained Immunity of Monocyte-Macrophage Populations in Osteoarthritis: Potential Molecular Links and Therapeutic Opportunities.}},
author = {Jian Zhang and Bingbing Chen and Yundong Xu and Heguo Yan and Niqin Xiao and Jing Xie and Zhaohu Xie and Zhaofu Li},
journal = {Cells},
year = {2026},
month = sep,
doi = {10.3390/cells15191756},
url = {https://europepmc.org/article/MED/42882454},
note = {CC BY},
}
RIS
TY - JOUR
TI - Damage-Associated Molecular Patterns and Trained Immunity of Monocyte-Macrophage Populations in Osteoarthritis: Potential Molecular Links and Therapeutic Opportunities.
AU - Jian Zhang
AU - Bingbing Chen
AU - Yundong Xu
AU - Heguo Yan
AU - Niqin Xiao
AU - Jing Xie
AU - Zhaohu Xie
AU - Zhaofu Li
PY - 2026
DA - 2026/09/26
JO - Cells
DO - 10.3390/cells15191756
UR - https://europepmc.org/article/MED/42882454
AB - Osteoarthritis (OA) is now widely discussed as a whole-joint immunometabolic disease involving cartilage, synovium, and subchondral bone, rather than as cartilage degeneration driven only by mechanical stress. Tissue injury, cell death, mitochondrial dysfunction, and extracellular matrix degradation can lead to the persistent release of damage-associated molecular patterns (DAMPs), which activate innate immune responses through pattern recognition receptors (PRRs). A key unresolved issue is why inflammation can persist or recur when there is no continuous external stimulus. Trained immunity provides an emerging framework for approaching this problem, with initial direct evidence now available in circulating monocytes from knee OA but broader validation still lacking. Following an initial stimulus and a subsequent resting interval, monocytes and macrophages may retain epigenetic and metabolic alterations that modify their responses to later homologous or heterologous challenges. This review summarizes the sources of DAMPs and their recognition mechanisms in the OA microenvironment, with particular attention to their potential links with trained immunity in monocyte-macrophage populations. We discuss PRR-mediated changes in chromatin accessibility, histone modifications, DNA methylation, and non-coding RNA regulation, as well as immunometabolic events such as enhanced glycolysis, tricarboxylic acid cycle remodeling, mitochondrial dysfunction, and accumulation of key metabolites. We also examine how monocyte-macrophage populations with persistent hyperresponsiveness after stimulus withdrawal and restimulation may contribute to persistent synovitis, cartilage matrix degradation, and abnormal subchondral bone remodeling. Finally, we summarize therapeutic opportunities potentially relevant to the proposed links between DAMP signaling and trained immunity. Recent evidence that high-mobility group box 1 (HMGB1) primes a trained phenotype in circulating monocytes provides initial direct support for DAMP-associated trained immunity in knee OA. However, its generalizability across independent cohorts, other DAMP classes, myeloid-cell compartments, disease stages, and OA phenotypes remains to be established.
SN - 2073-4409
ER -