{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:49:37Z","timestamp":1792090177005,"version":"4.4.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>\n                    <jats:list list-type=\"plain\">\n                      <jats:list-item>\n                        <jats:p>\u27a2 Osteoarthritis (OA) represents a biologically dynamic disease characterized by progressive failure of cartilage homeostasis through interconnected molecular mechanisms. Chondrocytes shift from an anabolic to a catabolic phenotype, marked by increased matrix metalloproteinase activity, while the synthetic capacity of articular cartilage diminishes.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\u27a2 Key signaling cascades including NF-\u03baB (nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPK (mitogen-activated protein kinase) become dysregulated, driving matrix degradation. Declining autophagy impairs cellular quality control while senescent cells accumulate, releasing inflammatory mediators that amplify tissue damage. The immune response extends beyond macrophage polarization to involve adaptive immune cells, including T cell subsets that sustain chronic synovial inflammation.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\u27a2 Emerging disease-modifying strategies\u2014including Wnt pathway inhibitors, FGF (fibroblast growth factor) 18 analogs, senolytic agents, gene therapy approaches, and allogeneic MSC (mesenchymal stem cell) implantation\u2014offer the first genuine prospects for altering the natural history of this disease. However, translational challenges remain, as highlighted by mixed results in recent clinical trials.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\u27a2 The future of OA management lies in precision molecular orthopaedics: matching patients to targeted therapies on the basis of their predominant disease endotype.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>","DOI":"10.2106\/jbjs.26.00446","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:01:21Z","timestamp":1792087281000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Mechanisms of Osteoarthritis"],"prefix":"10.2106","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6344-4417","authenticated-orcid":false,"given":"Alexander 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