Department of Materials Science and Engineering, Cornell University, Ithaca, New York, USA.
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
J Orthop Res. 2024 Jul;42(7):1438-1447. doi: 10.1002/jor.25793. Epub 2024 Jan 30.
Inflammation of the synovium, known as synovitis, plays an important role in the pathogenesis of osteoarthritis (OA). Synovitis involves the release of a wide variety of pro-inflammatory 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-established equine model of synovitis, this effective lubricating viscosity decreased by up to 10,000-fold for synovitis SF compared to a ~4 fold change in conventional viscosity measurements. Further, the effective lubricating viscosity was strongly inversely correlated (r = -0.6 to -0.8) to multiple established biochemical markers of SF inflammation, including white blood cell count, prostaglandin E (PGE), 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.
滑膜炎症，即滑膜炎，在骨关节炎（OA）的发病机制中起着重要作用。滑膜炎涉及到滑膜液（SF）中多种促炎介质的释放，这些介质会破坏关节软骨细胞外基质，并诱导软骨细胞死亡和凋亡。OA 炎症会极大地改变滑膜液的成分，包括透明质酸和润滑素的变化，它们是 SF 中的主要润滑分子。然而，关节炎症的关键生化标志物与 SF 的机械功能之间的关系尚不清楚。在这里，我们展示了一种新的分析框架在测量 SF 润滑软骨的有效粘度中的应用，该粘度与传统流变学粘度不同。值得注意的是，在一个成熟的马滑膜炎模型中，与传统粘度测量的约 4 倍变化相比，滑膜炎 SF 的有效润滑粘度降低了多达 10000 倍。此外，有效润滑粘度与多个 SF 炎症的既定生化标志物呈强烈的负相关（r = -0.6 至 -0.8），包括白细胞计数、前列腺素 E（PGE）和趋化因子配体（CCLs）浓度，而传统的粘度测量与这些标志物相关性较差。这些发现表明，需要采用实验和分析方法来表征滑液的功能润滑特性及其与可溶性生物标志物的关系，以更好地理解 OA 的进展。
