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Synovitis involves the release of a wide variety of pro\u2010inflammatory mediators in synovial fluid (SF) that damage the articular cartilage extracellular matrix and induce death and apoptosis in chondrocytes. The composition of synovial fluid is dramatically altered by inflammation in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF. However, the relationship between key biochemical markers of joint inflammation and mechanical function of SF is not well understood. Here, we demonstrate the application of a novel analytical framework to measure the effective viscosity for SF lubrication of cartilage, which is distinct from conventional rheological viscosity. Notably, in a well\u2010established equine model of synovitis, this effective lubricating viscosity decreased by up to 10,000\u2010fold for synovitis SF compared to a ~4 fold change in conventional viscosity measurements. Further, the effective lubricating viscosity was strongly inversely correlated (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.6 to \u22120.8) to multiple established biochemical markers of SF inflammation, including white blood cell count, prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>), and chemokine ligand (CCLs) concentrations, while conventional measurements of viscosity were poorly correlated to these markers. These findings demonstrate the importance of experimental and analytical approaches to characterize functional lubricating properties of synovial fluid and their relationships to soluble biomarkers to better understand the progression of OA.<\/jats:p>","DOI":"10.1002\/jor.25793","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T04:14:15Z","timestamp":1706674455000},"page":"1438-1447","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Loss of effective lubricating viscosity is the primary mechanical marker of joint inflammation in equine synovitis"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2910-9176","authenticated-orcid":false,"given":"Karan","family":"Vishwanath","sequence":"first","affiliation":[{"name":"Department of Materials Science and Engineering Cornell University Ithaca New York 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