{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:57:24Z","timestamp":1782953844167,"version":"3.54.5"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Osteoarthritis (OA) is a prevalent degenerative disorder affecting joints, characterized by progressive cartilage deterioration, inflammation of the synovium, and structural damage to subchondral bone. Inflammation mediated by synovial macrophages is a key driver of OA progression. Emerging evidence indicates that macrophage ferroptosis in inflamed synovium plays a pivotal role in disease advancement. 7-Dehydrocholesterol (7-DHC), an endogenous sterol with potent antioxidant properties due to its conjugated diene structure, effectively inhibits lipid peroxidation and ferroptosis. This study aimed to investigate whether 7-DHC delays OA progression by suppressing oxidative stress, inflammatory responses, and ferroptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To explore the mechanisms underlying inflammation\n                      <jats:italic>in vitro<\/jats:italic>\n                      , RAW 264.7 macrophages were stimulated using lipopolysaccharide (LPS). The effects of 7-DHC treatment were subsequently evaluated by measuring reactive oxygen species (ROS) production, levels of inflammatory cytokines, and expression of ferroptosis-related proteins including GPX4 and ACSL4. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunofluorescence (IF), and Western blotting (WB) techniques were utilized to clarify the associated molecular pathways. Additionally, to verify the\n                      <jats:italic>in vivo<\/jats:italic>\n                      efficacy, an OA mouse model was established by administering complete Freund\u2019s adjuvant (CFA) into the joint cavity, enabling assessment of inflammatory changes in synovial tissues and bone structural modifications following 7-DHC intervention.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The findings from RAW 264.7 macrophages stimulated with LPS indicated significant inhibition of ROS accumulation, downregulation of pro-inflammatory cytokines such as TNF-\u03b1 and IL-1\u03b2, and normalization of ferroptosis-associated protein expression patterns after 7-DHC application. Additionally, 7-DHC markedly suppressed phosphorylation of MAPK\/NF-\u03baB pathway proteins while enhancing expression of Nrf2\/HO-1 pathway proteins.\n                      <jats:italic>In vivo<\/jats:italic>\n                      experiments confirmed that 7-DHC significantly reduced inducible nitric oxide synthase (iNOS) expression in inflamed synovial tissue, promoted expression of GPX4, a key lipid peroxidation inhibitor, and improved the oxidative stress environment of synovial tissues. Consequently, knee joint inflammation and bone destruction were markedly alleviated in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>7-DHC exerts anti-inflammatory and antioxidant effects by inhibiting the ROS\/MAPK\/NF-\u03baB pathway and activating the Nrf2\/HO-1 pathway. This reduces oxidative damage, inflammation, and ferroptosis in macrophages, thereby delaying OA progression. As a promising therapeutic strategy, 7-DHC may provide new research directions and clinical translational opportunities for OA treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1760112","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T06:50:13Z","timestamp":1770360613000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["7-Dehydrocholesterol attenuates osteoarthritis by synergistically inhibiting oxidative stress, inflammation, and ferroptosis in macrophages"],"prefix":"10.3389","volume":"17","author":[{"given":"Wenchao","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Stomatology, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengru","family":"Hua","sequence":"additional","affiliation":[{"name":"Graduate School, Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Stomatology, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxin","family":"Sun","sequence":"additional","affiliation":[{"name":"Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuheng","family":"Pan","sequence":"additional","affiliation":[{"name":"Shanghai Ninth People\u2019s Hospital, College of Stomatology, Shanghai Jiao Tong University; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Miao","sequence":"additional","affiliation":[{"name":"Shanghai Ninth People\u2019s Hospital, College of Stomatology, Shanghai Jiao Tong University; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuzhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Ninth People\u2019s Hospital, College of Stomatology, Shanghai Jiao Tong University; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology","place":["Shanghai, China"]},{"name":"Department of Oral Surgery, Shanghai Ninth People\u2019s Hospital, College of Stomatology, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Stomatology, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.mcna.2019.10.007","article-title":"Osteoarthritis: pathology, diagnosis, and treatment options","volume":"104","author":"Abramoff","year":"2020","journal-title":"Med. 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