The Mechanism of Articular Cartilage Degeneration in Osteoarthritis and Rheumatoid Arthritis

为了探讨骨性关节炎和类风湿关节炎患者关节软骨退行性变的机制，我们进行了免疫组织化学和生化研究。针对II型胶原中溴化氰肽（CB）的多克隆抗体可与人II型胶原的未缠绕α链和CB衍生肽发生特异性反应，用于鉴定关节软骨中II型胶原纤维的降解。在轻度退变的人骨关节炎软骨中，抗cb肽抗体在浅表纤颤和浅表和中区间基质中发现最突出的染色。相反，这些区域被抗II型胶原抗体和抗蛋白多糖抗体染色较弱。浅表区细胞团周围可见抗纤维连接蛋白抗体和抗硫酸皮肤蛋白多糖抗体染色。另一方面，类风湿关节炎患者关节软骨深部区抗cb肽抗体染色良好。用从骨关节炎和类风湿关节炎软骨中获得的培养软骨细胞也研究了II型胶原和蛋白聚糖的合成。来自轻度退行性骨关节炎软骨的软骨细胞合成活性增加，而来自中度退行性软骨的细胞合成活性降低。类风湿性关节炎的软骨细胞合成II型胶原蛋白和蛋白多糖分子水平降低。这些结果表明，骨关节炎软骨的退变始于浅表区，然后逐渐进展到中、深部区，而类风湿关节炎软骨的退变始于深部区。

Immunohistochemical and biochemical studies were undertaken in order to investigate the mechanism of articular cartilage degeneration if patients with osteoarthritis and rheumatoid arthritis. Polyclonal antibodies against cyanogen bromide (CB) peptide of Type II colagen that specifically react with unwound alpha-chains and CB-derived peptides of human Type II collagen were utilized to identify degradation of Type II collagen fibers in articular cartilage. In the case of human osteoarthritic cartilage with mild degeneration, the most prominent staining by the anti-CB peptide antibodies was found in the superficial fibrillation and in the interterritorial matrix of the superficial and mid-zones. Incontrast, these regions showed weak staining by both anti-Type II collagen antibodies and anti-proteoglycan antibodies. Moreover, Staining by anti-fibronectin antibodies and anti-dermatan sulfate proteoglycan antibodies was observed around cell clusters in the superficial zone. On the other hand, in the case of rheumatoid arthritis, deep zone of the articular cartilage was well stained by the anti-CB peptide antibodies.Synthesis of the Type II collagen and proteoglycans was also investigated using cultured human chondrocytes obtained from osteoarthritic and rheumatoid arthritis cartilage. Chondrocytes from mildly degenerated osteoarthritic cartilage showed increased synthetic activity, while cells from moderately degenerated cartilage showed decreased activity. Chondrocytes from rheumatoid arthritis were found to synthesize decreased level of Type II collagen and proteoglycan molecules.These findings indicate that degeneration in osteoarthritic cartilage was initiated in the superficial zone and then gradually progressed to the mid and deep zones, While degeneration in the rheumatoid arthritic cartilage was initiated in the deep zone.