{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:56:58Z","timestamp":1792598218413,"version":"4.5.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To explore the role and underlying mechanism of mitochondrial transcription elongation factor TEFM in osteoarthritis (OA) cartilage degeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>in vitro<\/jats:italic>\n                      inflammatory injury model was established by interleukin-1\u03b2 (IL-1\u03b2) 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\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      rescue assays were employed to elucidate TEFM-mediated signaling cascades. For\n                      <jats:italic>in vivo<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TEFM expression was significantly upregulated in OA cartilage, and MR analysis supported a potential causal association with knee OA risk.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments demonstrated that TEFM knockdown ameliorated chondrocyte dysfunction, attenuated mitochondrial oxidative stress, and suppressed AKT\/NF-\u03baB pathway activation. Mechanistically, NAC treatment and H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      rescue assays verified that ROS serve as a critical upstream mediator linking TEFM to AKT\/NF-\u03baB signaling, and specific inhibitor assays further confirmed the functional necessity of the AKT\/NF-\u03baB cascade in TEFM-mediated chondrocyte injury.\n                      <jats:italic>In vivo<\/jats:italic>\n                      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-\u03baB pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TEFM facilitates OA cartilage degeneration via the ROS-AKT\/NF-\u03baB axis, which provides a novel therapeutic target for OA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1961836","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T04:47:53Z","timestamp":1791348473000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TEFM drives cartilage degeneration in osteoarthritis via the ROS-AKT\/NF-\u03baB signaling axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Kanghua","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Sports Medicine, Orthopaedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]},{"name":"Ganzhou Hospital-Nanfang Hospital, Southern Medical University (Ganzhou People\u2019s Hospital)","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meifeng","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, Orthopaedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runting","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, Orthopaedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, Orthopaedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, Orthopaedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guicai","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, Orthopaedic Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00163-7","article-title":"Global, regional, and national burden of osteoarthritis, 1990-2020 and projections to 2050: A systematic analysis for the global burden of disease study 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