Etipathogenesis of osteoarthritis and cartilage proteoglycan.

本研究包括关节软骨中蛋白多糖的形态学、生物化学和免疫学工作，对软骨特征蛋白多糖合成遗传失败但型胶原合成正常的CMD/CMD小鼠骨骺软骨结构进行光镜和电镜观察<II>，发现胶原纤维明显异常：例如胶原纤维的直径增加、周期性条带图案的出现和褶皱形成。这些结果表明，软骨特征性蛋白聚糖（Cartilage-characteristic proteoglycan，CartilagePG）通常限制胶原纤维的侧向生长，并影响体内胶原纤维的形成。免疫荧光染色显示，突变细胞的结节与正常细胞不同，缺乏软骨PG，型胶原沉积不均匀和减少<II>。外源性添加的软骨PG从正常小鼠软骨或群大鼠软骨肉瘤的培养基中制备的被纳入专门的细胞外基质的结节，同时纠正型胶原蛋白的异常分布模式<II>。软骨PG与基质的结合受到透明质酸或十糖的干扰，结果表明软骨PG的完整形式是特异性结合到软骨细胞结节中所必需的，并进一步表明软骨PG在基质大分子组装中起调节作用。

The research includes morphological, biochemical and immunological work about the proteoglycan in articular cartilage.Light and electron microscopic observations on the structure of epiphyseal cartilages in the cmd/cmd mice, which had genetically failed to synthesize cartilage-characteristic proteoglycan but were normal in type <II> collagen synthesis, showed apparent abnormalities of collagen fibrils: e.g. increase in the diameter, appearance of periodic banding patterns and bundle-formation of collagen fibrils. These findings suggest that cartilage-characteristic proteoglycan (Cartilage PG) normally limits the lateral growth of collagen fibrils and affects collagen fibrillogenesis in vivo.Chondrocytes from the cmd/cmd cartilage cultured in vitro produced nodules with greatly reduced extracellular matrix. Immunofluorescence staining revealed that the nodules of mutant cells differed from the normal in lacking cartilage PG and in uneven and reduced deposition of type <II> collagen. Exogenously added cartilage PG prepared from either normal mouse cartilage or Swarm rat chondrosarcoma to the culture medium was incorporated exclusively into the extracellular matrices of the nodules, with a concurrent correction of the abnormal distribution pattern of type <II> collagen. The incorporation of cartilage PG into the matrix was disturbed by hyaluronic acid or decasaccharide.The results indicate that the intact from of cartilage PG is required for specific incorporation into the chondrocyte nodules, and further suggest that cartilage PG plays a regulatory role in the assembly of the matrix macromolecules.