Noyori K, Jasin H E
University of Arkansas for Medical Sciences, Little Rock 72205.
Arthritis Rheum. 1994 Nov;37(11):1656-63. doi: 10.1002/art.1780371115.
Recent studies from our laboratory have identified the nonaggregating, collagen-binding proteoglycans, fibromodulin (FM) and decorin, and fibronectin (Fn) and albumin, noncovalently bound at the articular surface of cartilage. The present studies were designed to investigate the interactions between these cartilage macromolecules and the underlying collagen matrix and their role as a barrier to cell adhesion in intact articular cartilage.
Cell adhesion studies were carried out with human skin fibroblasts incubated on the articular surface of bovine cartilage explants and on collagen-coated and/or Fn-coated plastic surfaces. Interactions of collagen and Fn with either FM or decorin were studied by radioimmunoassay of the same surfaces, using specific antibodies.
The present studies show that 1) Fn is immunologically detectable at the intact articular surface of cartilage; 2) fibroblast adhesion to Fn is inhibited by cartilage surface extract proteins and by purified FM, but not by purified decorin; 3) FM has binding affinity for Fn; 4) FM interferes with the binding of a monoclonal antibody specific for the cell-binding domain of Fn; and 5) FM and decorin inhibit collagen-dependent fibroblast adhesion.
These results indicate that the small proteoglycans at the normal articular surface may act as a barrier to cell adhesion. Since protective cartilage surface proteins break down readily after the induction of acute arthritis in experimental animals, and in rheumatoid cartilage specimens, it is postulated that proteolytic degradation of the surface proteoglycans may be responsible for increasing cell adhesion to, and subsequent pannus invasion of, articular cartilage in inflammatory arthritis.
我们实验室最近的研究已鉴定出在软骨关节表面非共价结合的非聚集性胶原结合蛋白聚糖、纤维调节素（FM）和核心蛋白聚糖，以及纤连蛋白（Fn）和白蛋白。本研究旨在探讨这些软骨大分子与下层胶原基质之间的相互作用，以及它们在完整关节软骨中作为细胞黏附屏障的作用。
用人皮肤成纤维细胞在牛软骨外植体的关节表面以及胶原包被和/或Fn包被的塑料表面上进行细胞黏附研究。使用特异性抗体，通过对相同表面进行放射免疫测定来研究胶原和Fn与FM或核心蛋白聚糖之间的相互作用。
本研究表明：1）在软骨完整的关节表面可通过免疫检测到Fn；2）软骨表面提取物蛋白和纯化的FM可抑制成纤维细胞对Fn的黏附，但纯化的核心蛋白聚糖则无此作用；3）FM对Fn具有结合亲和力；4）FM干扰对Fn细胞结合域具有特异性的单克隆抗体的结合；5）FM和核心蛋白聚糖抑制胶原依赖性成纤维细胞黏附。
这些结果表明，正常关节表面的小蛋白聚糖可能作为细胞黏附的屏障。由于在实验动物诱导急性关节炎后以及类风湿性软骨标本中，保护性软骨表面蛋白容易分解，因此推测表面蛋白聚糖的蛋白水解降解可能是炎症性关节炎中细胞对关节软骨黏附增加以及随后血管翳侵入的原因。
