Transcriptomic Identification and Validation of NDUFS2 in Acute Rat TMJ Synovitis and Its Functional Role in LPS-Induced Synovial Fibroblast Inflammation.

Authors

Jinghan Li, Jingpeng Zuo, Jianduan Liang, Changbin Zhang, Tao Xie, Feifei Xie, Yinzi Xin, Wei Wang

Published in

Journal of inflammation research. Volume 19. Pages 614759. Epub Oct 02, 2026.

Abstract

Temporomandibular joint (TMJ) synovitis persistently drives TMJ osteoarthritis (TMJOA) progression. Aberrant reactive oxygen species (ROS) accumulation triggers chronic oxidative stress, amplifying synovial inflammation. This study aimed to identify candidate ROS-related genes through transcriptomic screening and explore their potential functional involvement in TMJ synovitis.
Acute TMJ synovitis was induced in male Sprague-Dawley rats via intra-articular injection of Complete Freund's Adjuvant (CFA). RNA sequencing of inflamed and normal synovial tissues was performed to screen target genes by intersecting differentially expressed genes (DEGs) with ROS-related genes (ROS-RGs). The expression of the candidate gene was validated in vivo and in vitro, and in vitro functional assays were performed using lipopolysaccharide (LPS)-induced synovial fibroblasts (SFs). The functions of NDUFS2 were assessed via siRNA knockdown or plasmid overexpression, supplemented by rescue experiments using the mitochondria-targeted antioxidant Mito-TEMPO. Intracellular ROS, mitochondrial ROS (mtROS), mitochondrial membrane potential (ΔΨm), and pro-inflammatory markers (MMP13, IL-1β, TNF-α) were evaluated.
NDUFS2 was identified as a candidate ROS-related gene through transcriptomic screening, and Gene Set Enrichment Analysis (GSEA) linked it to signaling pathways including oxidative phosphorylation. NDUFS2 was markedly upregulated in inflamed TMJ synovial tissues and LPS-stimulated SFs. In the LPS-induced model, NDUFS2 knockdown attenuated ROS/mtROS accumulation, partially restored ΔΨm, and reduced pro-inflammatory marker expression, whereas NDUFS2 overexpression could increase ROS/mtROS levels, reduce ΔΨm, and elevate pro-inflammatory marker expression. Furthermore, rescue experiments demonstrated that scavenging mtROS with Mito-TEMPO reversed NDUFS2-mediated oxidative stress and inflammation.
Our findings identify NDUFS2 as a key ROS-related gene associated with acute TMJ synovitis through transcriptomic screening. In vitro evidence indicates that NDUFS2 modulates inflammatory responses in synovial fibroblasts via mtROS-mediated mitochondrial oxidative stress. These findings provide an experimental basis for further exploration of TMJ synovitis pathogenesis.

PMID:
42841081
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.

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