Previously submitted to: JMIR Biomedical Engineering (no longer under consideration since Jul 14, 2026)
Date Submitted: May 25, 2026
Open Peer Review Period: May 25, 2026 - Jul 20, 2026
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Immuno-Metabolic Crosstalk in Osteoarthritis: From Mechanisms to Therapies
ABSTRACT
Background:
Osteoarthritis (OA) has traditionally been viewed as a degenerative joint disease characterized by cartilage deterioration. However, growing evidence indicates that OA is better understood as a systemic immune-metabolic disorder driven by the interplay of metabolic dysregulation, chronic low-grade inflammation, and abnormal immune activation.
Objective:
This review summarizes the bidirectional crosstalk between immunity and metabolism during OA progression.
Methods:
Immune cells, especially macrophages and T cells, contribute to cartilage degradation and synovial inflammation through the release of pro-inflammatory mediators. At the same time, metabolic abnormalities, including mitochondrial dysfunction, aberrant glycolysis, and lipid dysregulation, disturb chondrocyte homeostasis and further amplify inflammatory responses by modulating immune function, thereby forming a self-perpetuating vicious cycle.
Results:
Based on this framework, emerging immunometabolic therapeutic strategies are discussed, including interventions targeting AMPK/mTOR signaling and key enzymes involved in glycolysis and lipid metabolism, as well as advanced biological approaches such as gene editing, synthetic biology, and stem cell-based therapies.
Conclusions:
Integrating multi-omics technologies with personalized medicine may enable precise patient stratification and dynamic monitoring, supporting a shift from symptomatic management to disease modification in OA. Future research should focus on clarifying the dynamic immunometabolic network underlying OA and promoting the clinical translation of innovative strategies through artificial intelligence and interdisciplinary collaboration.
Citation
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