Authors
Yifan Yu, Taihe Liu, Chenhao Pan, Haopeng Sun, Zhipeng Chen, Haoxian Liu, Wingcheuk Ko, Siyuan Tan, Jiankai Luo, Shixun Li, Changchuan Li, Yue Ding
Published in
Cell communication and signaling : CCS. Volume 24. Issue 1. Apr 16, 2026. Epub Apr 16, 2026.
Abstract
Prosthetic wear particle-driven macrophage inflammation severely limits the long-term efficacy of total joint replacements by causing aseptic loosening. However, the specific mechanisms by which wear particles induce macrophage inflammation remain incompletely elucidated. Itaconic acid produced by the Krebs cycle is markedly up-regulated in TiPs-stimulated macrophages, which may modulate mitochondrial metabolism through protein itaconation or competitive inhibition. Here, using 4-OI, we demonstrate that itaconate functions as an endogenous metabolic regulator that suppresses SDH activity, thereby significantly inhibiting STING pathway activation. Moreover, 4-OI can alkylate STAT1, preventing its phosphorylation and relieving transcriptional repression of the mitochondrial transcription factor TFAM, which stabilizes mitochondrial homeostasis and attenuates macrophage inflammation. In a murine calvarial osteolysis model, 4-OI reversed bone destruction induced by TiPs and TFAM knockdown. Collectively, our findings establish itaconate as a critical endogenous metabolite that alleviates wear particle–mediated inflammation and osteolysis by reprogramming macrophage metabolism.
The online version contains supplementary material available at 10.1186/s12964-026-02874-4.
PMID:
41992317
Bibliographic data and abstract were imported from PubMed on 16 Jun 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 13
- Comments 0