IMMUNOPROBES FOR LUBRICIN FROM HUMAN SYNOVIAL FLUID

尽管进行了大量的研究，但在骨性关节炎的发病机制中具体或相关的原因仍不清楚。这证明有理由对退行性关节疾病涉及的其他因素进行新的研究。关节润滑学-生物摩擦学的研究一直充满着相互矛盾的理论，未能充分利用分子技术，标准化商业检测，并赋予滑液润滑的临床重要性。本研究针对动物关节滑膜润滑的分子机制进行了研究。大量文献表明，这些摩擦和加压表面(即轴承)具有低摩擦性能(1-4)。这些特性在一定程度上源于关节软骨的滑滑性。大多数报告实际上涉及滑液的流变学，并可能错误地假设其粘度是关节润滑的基础(5-10)。直接测量证明，滑液降低了软骨轴承和某些人工表面之间的摩擦系数。滑液中的一种被称为“润滑素”的润滑性糖蛋白对此负有责任，但还没有人提出它是如何发挥作用的机制，或者如何在体外对其进行研究。PI使用了一种由乳胶和玻璃组成的关节摩擦计，复制了以前使用软骨轴承进行的研究的关键发现。它隔离了以前别人使用的边界模式润滑测量装置。滑液、唾液和清洁剂是唯一显示这种活性的物质(11)。润滑剂对乳胶玻璃轴承的润滑是PI最近发现的。这提供了一个实验机会，可以将失败的润滑与大量患者的退行性关节疾病的发生联系起来，并将这一措施与润滑剂因果联系起来。低摩擦系数(Mu)不一定是防磨损的指标，但滑液确实赋予软骨这种特性(12)。目前尚不清楚润滑剂的缺乏或缺乏是否对骨关节炎或类风湿性关节炎的初始或持续发病机制有重要意义。这项研究的主要目的是开发新的免疫学探针，并用这些探针确定从健康和关节炎患者关节提取的滑液中润滑剂的浓度。

Specific or related causes in the pathogenesis of osetoarthritis remain unclear despite a great deal of investigation. This justifies a new venue of research into other factors involved in degenerative joint disease . The study of joint lubrication, biotribology, has been fraught with conflicting theories, failure to adequately use molecular techniques, standardize merchanical assays and assign clinical importance to lubrication by synovial fluid. This investigation addresses the molecular of synovial lubrication of animal joints. A considerable literature has demonstrated that these rubbing and pressurized surfaces (i.e., bearings) have low frictional properties (1-4). These properties arise in part from the slippery nature of articular cartilage. Most reports actually deal with the rheology of synovial fluid and may incorrectly assume that its viscosity is the basis for joint lubrication (5-10). Direct measurements documents that synovial fluid lowers the coefficient of friction between cartilage bearings and certain artificial surfaces. A lubricating glycoprotein termed "lubricin" from synovial fluid is responsible for this but no one has proposed a mechanism of how it does so or how to study it in vitro. An arthrotripsometer composed of latex oscillating against glass employed by the PI reproduced critical findings of previous studies using cartilage bearings. It isolated boundary mode lubrication measuring devices previously employed by others. Synovial fluid, saliva, and detergents are the only substances which display this activity (11). The observation that lubricin lubricated the latex: glass bearing is a recent discovery by the PI. This provides an experimental opportunity to implicate failed lubrication in the occurrence of degenerative joint disease in a large number of patients and to causally link this measure to lubricin. A low coefficient of friction (mu) is no necessarily a measure of wear protection but synovial fluid does in fact confer this property to cartilage (12). It is unknown if the absence or paucity of lubricin is significant to the initial or continued pathogenesis of either osteoarthritis or rheumatoid arthritis. This principal goal of this investigation is to develop new immunological probes and with these identify the concentration of lubricin in synovial fluid extracted from healthy and arthritic human joints.