TEFM drives cartilage degeneration in osteoarthritis via the ROS-AKT/NF-κB signaling axis
- 1Department of Sports Medicine, Orthopaedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University
- 2Ganzhou Hospital-Nanfang Hospital, Southern Medical University (Ganzhou People’s Hospital)
Abstract
Objective: To explore the role and underlying mechanism of mitochondrial transcription elongation factor TEFM in osteoarthritis (OA) cartilage degeneration.
Methods: Bioinformatics analysis based on the GSE114007 human knee cartilage dataset and two-sample Mendelian randomization (MR) analysis were performed to evaluate the association between TEFM and knee OA. Human cartilage specimens were collected to verify TEFM expression patterns. Lentivirus-mediated TEFM knockdown was performed in ATDC5 chondrocytes, and an in vitro inflammatory injury model was established by interleukin-1β (IL-1β) stimulation. The effects of TEFM on chondrocyte function were determined by RT-qPCR, Western blotting, toluidine blue staining, and immunofluorescence staining. Transcriptome sequencing (RNA-seq), reactive oxygen species (ROS) scavenging, specific pathway inhibition, and H ₂ O ₂ rescue assays were employed to elucidate TEFM-mediated signaling cascades. For in vivo validation, a destabilization of the medial meniscus (DMM)-induced OA mouse model was established, and adeno-associated virus serotype 9 carrying sh-TEFM (AAV9-sh-TEFM) was administered via intra-articular injection. Pathological changes in cartilage and subchondral bone were assessed by micro-CT and histological staining.
Results: TEFM expression was significantly upregulated in OA cartilage, and MR analysis supported a potential causal association with knee OA risk. In vitro experiments demonstrated that TEFM knockdown ameliorated chondrocyte dysfunction, attenuated mitochondrial oxidative stress, and suppressed AKT/NF-κB pathway activation. Mechanistically, NAC treatment and H ₂ O ₂ rescue assays verified that ROS serve as a critical upstream mediator linking TEFM to AKT/NF-κB signaling, and specific inhibitor assays further confirmed the functional necessity of the AKT/NF-κB cascade in TEFM-mediated chondrocyte injury. In vivo studies revealed that intra-articular TEFM silencing alleviated cartilage degeneration and subchondral bone pathological damage in OA mice, accompanied by inhibition of the AKT/NF-κB pathway.
Conclusion: TEFM facilitates OA cartilage degeneration via the ROS-AKT/NF-κB axis, which provides a novel therapeutic target for OA.
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BibTeX
@article{yang2026tefm,
title = {{TEFM drives cartilage degeneration in osteoarthritis via the ROS-AKT/NF-κB signaling axis}},
author = {Kanghua Yang and Meifeng Lu and Runting Xiao and Shuai Xu and Yulong Ouyang and Guicai Sun},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1961836},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1961836/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - TEFM drives cartilage degeneration in osteoarthritis via the ROS-AKT/NF-κB signaling axis
AU - Kanghua Yang
AU - Meifeng Lu
AU - Runting Xiao
AU - Shuai Xu
AU - Yulong Ouyang
AU - Guicai Sun
PY - 2026
DA - 2026/10/07
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1961836
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1961836/full
AB - Objective: To explore the role and underlying mechanism of mitochondrial transcription elongation factor TEFM in osteoarthritis (OA) cartilage degeneration. Methods: Bioinformatics analysis based on the GSE114007 human knee cartilage dataset and two-sample Mendelian randomization (MR) analysis were performed to evaluate the association between TEFM and knee OA. Human cartilage specimens were collected to verify TEFM expression patterns. Lentivirus-mediated TEFM knockdown was performed in ATDC5 chondrocytes, and an in vitro inflammatory injury model was established by interleukin-1β (IL-1β) stimulation. The effects of TEFM on chondrocyte function were determined by RT-qPCR, Western blotting, toluidine blue staining, and immunofluorescence staining. Transcriptome sequencing (RNA-seq), reactive oxygen species (ROS) scavenging, specific pathway inhibition, and H ₂ O ₂ rescue assays were employed to elucidate TEFM-mediated signaling cascades. For in vivo validation, a destabilization of the medial meniscus (DMM)-induced OA mouse model was established, and adeno-associated virus serotype 9 carrying sh-TEFM (AAV9-sh-TEFM) was administered via intra-articular injection. Pathological changes in cartilage and subchondral bone were assessed by micro-CT and histological staining. Results: TEFM expression was significantly upregulated in OA cartilage, and MR analysis supported a potential causal association with knee OA risk. In vitro experiments demonstrated that TEFM knockdown ameliorated chondrocyte dysfunction, attenuated mitochondrial oxidative stress, and suppressed AKT/NF-κB pathway activation. Mechanistically, NAC treatment and H ₂ O ₂ rescue assays verified that ROS serve as a critical upstream mediator linking TEFM to AKT/NF-κB signaling, and specific inhibitor assays further confirmed the functional necessity of the AKT/NF-κB cascade in TEFM-mediated chondrocyte injury. In vivo studies revealed that intra-articular TEFM silencing alleviated cartilage degeneration and subchondral bone pathological damage in OA mice, accompanied by inhibition of the AKT/NF-κB pathway. Conclusion: TEFM facilitates OA cartilage degeneration via the ROS-AKT/NF-κB axis, which provides a novel therapeutic target for OA.
SN - 1664-3224
ER -