Binding and localization of recombinant lubricin to articular cartilage surfaces
Binding and localization of recombinant lubricin to articular cartilage surfaces
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DOI：
10.1002/jor.20325
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发表时间：
2007-03-01
影响因子：
2.8
通讯作者：
Flannery, Carl R.
中科院分区：
文献类型：
--
作者：
Jones, Aled R. C.;Gleghorn, Jason P.;Flannery, Carl R.
润滑素是一种分泌的细胞保护性糖蛋白，有助于维持关节软骨表面低摩擦水平所必需的基本边界润滑机制。因此，润滑素功能的减少被认为是退行性关节疾病如骨关节炎的不利影响因素。润滑素作为滑液的可溶性组分存在，并且在关节软骨的浅表层中合成和定位（并且因此也被描述为“浅表区蛋白”或SZP）;然而，负责润滑素在该部位的保留的定义的相互作用没有被很好地表征。在目前的研究中，我们确定了分子决定因素，使润滑素有效地结合到关节软骨表面。观察到滑膜润滑素以及重组全长润滑素和包含润滑素G末端（血结合蛋白样）结构域（LUB-C，由外显子7-12编码）的蛋白质构建体与浅表区的有效和特异性结合。代表润滑素的N-末端区域（LUB-N，由外显子2-5编码）的构建体没有表现出明显的软骨结合能力，但显示出二聚化的能力，从而潜在地影响润滑素聚集。二硫键破坏显着衰减重组润滑素和LUB-C结合软骨表面，证明蛋白质二级结构的要求，以促进润滑素在相关组织界面的适当定位。这些发现有助于确定有助于润滑素功能的其他关键属性，预计这将有助于维持关节内稳态。(c)2006骨科研究学会。出版社：Wiley Periodicals，Inc.
Lubricin is a secreted, cytoprotective glycoprotein that contributes to the essential boundary lubrication mechanisms necessary for maintaining low friction levels at articular cartilage surfaces. Diminishment of lubricin function is thereby implicated as an adverse contributing factor in degenerative joint diseases such as osteoarthritis. Lubricin occurs as a soluble component of synovial fluid, and is synthesized and localized in the superficial layer of articular cartilage (and thus has also been described as "superficial zone protein", or SZP); however, defined interactions responsible for lubricin retention at this site are not well characterized. In the current studies, we identified molecular determinants that enable lubricin to effectively bind to articular cartilage surfaces. Efficient and specific binding to the superficial zone was observed for synovial lubricin, as well as for recombinant full-length lubricin and a protein construct comprising the lubricin G terminal (hemopexin-like) domain (LUB-C, encoded by exons 7-12). A construct representing the N-terminal region of lubricin (LUB-N, encoded by exons 2-5) exhibited no appreciable cartilage-binding ability, but displayed the capacity to dimerize, and thus potentially influence lubricin aggregation. Disulfide bond disruption significantly attenuated recombinant lubricin and LUB-C binding to cartilage surfaces, demonstrating a requirement for protein secondary structure in facilitating the appropriate localization of lubricin at relevant tissue interfaces. These findings help identify additional key attributes contributing to lubricin functionality, which would be expected to be instrumental in maintaining joint homeostasis. (c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.