{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:27:16Z","timestamp":1788409636029,"version":"build-2803163510"},"reference-count":42,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["CARTILAGE"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To investigate the regulatory role of Toll-like receptor 3 (TLR3) in osteoarthritis (OA) progression, particularly its impacts on cartilage degradation, NF-\u03baB-mediated inflammation, and autophagy activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method:<\/jats:title>\n                    <jats:p>1. Model Constuction: OA mouse model generated via anterior cruciate ligament transection (ACLT); LPS-induced inflammatory injury in murine ATDC5 chondrocytes; Histomorphological analysis of cartilage tissue using H&amp;E and Safranine O staining. 2. Molecular Detection: TLR3 expression assessed by Western blot; Cartilage degradation markers (MMP-13, ADAMTS) and NF-\u03baB pathway proteins analyzed via Western blot; Pro-inflammatory cytokine levels (IL-1\u03b2, TNF-\u03b1) quantified via RT-qPCR and Western blot. 3. Functional Assays: Cell viability examined via CCK-8 assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>1. TLR3 Upregulation: TLR3 was highly expressed in OA cartilage and LPS-treated chondrocytes. 2. Cartilage Protection: TLR3 inhibition reduced cartilage erosion and proteoglycan loss in ACLT mice (confirmed by H&amp;E and Safranine O staining); Downregulation of cartilage degradation markers (MMP-13, ADAMTS-5) observed in TLR3-knockdown models. 3. Anti-inflammatory Effects: TLR3 knockdown suppressed NF-\u03baB activation, reducing IL-1\u03b2 and TNF-\u03b1 levels. 4. Autophagy Activation: Enhanced LC3-II\/LC3-I ratio and Beclin-1 expression indicated TLR3 inhibition promotes autophagy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>TLR3 drives OA progression through dual mechanisms: 1. Pro-inflammatory Pathway: Activates NF-\u03baB signaling to amplify cytokine release and cartilage matrix breakdown. 2. Autophagy Suppression: Inhibits autophagy-related proteins, impairing cellular homeostasis. Targeting TLR3 may represent a therapeutic strategy to balance inflammation and autophagy, potentially slowing OA progression in multi-joint involvement cases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/19476035251317713","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T12:09:06Z","timestamp":1750766946000},"page":"783-793","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Inhibition of Toll-Like Receptor 3 Relieves Osteoarthritis by Suppression of Cartilage Degradation, Nuclear Factor Kappa B\u2013Mediated Inflammation, and Activation of Autophagy"],"prefix":"10.1177","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8913-3658","authenticated-orcid":false,"given":"Zhe","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Jiangyin Huiyou Orthopedics Hospital, Wuxi, P.R. 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