Little C B, Ghosh P
Raymond Purves Bone and Joint Research Laboratories, Royal North Shore Hospital, University of Sydney, St Leonards, NSW, Australia.
Osteoarthritis Cartilage. 1997 Jan;5(1):49-62. doi: 10.1016/s1063-4584(97)80031-3.
In this study we investigated the hypothesis that cartilage from defined regions of ovine stifle joints, which were subjected to differing mechanical stresses, contained phenotypically distinct chondrocyte populations. Chondrocyte phenotypes were identified by the relative biosynthesis of the proteoglycans (PGs) aggrecan, biglycan and decorin. Articular cartilage (AC) from adult and neonatal ovine stifle joints were examined. Cells were cultured as both full-depth AC explants and in alginate beads after their isolation from the AC matrix. When chondrocytes from the various topographical regions of adult ovine knee joints were cultured as explants they demonstrated a consistent difference with regard to the metabolism of aggrecan and decorin. Significantly, this topographically-dependent phenotypic expression of PGs was preserved when the chondrocytes were cultured in alginate beads. In adult joints, chondrocytes from the central region of the tibial plateau not covered by the meniscus, which is subjected to high mechanical loads in-vivo, synthesized less aggrecan but more decorin than cells from regions covered by the meniscus. When chondrocytes from identical AC regions of neonatal ovine joints were cultured as explants, no topographical difference in aggrecan nor decorin metabolism could be detected. The results of this study, in association with the existing literature, lead us to propose that post-natal mechanical loading of AC could select for chondrocyte clones or induce a lasting modulation of chondrocyte phenotypic expression in different joint regions. Such cellular changes could result in the synthesis of PG populations that confer properties to AC most suited to resist the variable mechanical stresses in the different joint regions. This study serves to emphasize the importance of using cartilage from identical joint areas when examining PG metabolism by chondrocytes. Further investigation into the relationship between mechanical loading, regional chondrocyte phenotype selection and the response of these cells to anabolic and catabolic factors may provide important insights into the focal nature of AC degeneration in osteoarthritis.
在本研究中，我们探讨了以下假说：绵羊 stifle 关节特定区域的软骨，由于承受不同的机械应力，含有表型不同的软骨细胞群体。通过蛋白聚糖（PGs）聚集蛋白聚糖、双糖链蛋白聚糖和核心蛋白聚糖的相对生物合成来鉴定软骨细胞表型。对成年和新生绵羊 stifle 关节的关节软骨（AC）进行了检查。细胞从 AC 基质中分离后，既作为全层 AC 外植体培养，也在藻酸盐珠中培养。当将成年绵羊膝关节不同地形区域的软骨细胞作为外植体培养时，它们在聚集蛋白聚糖和核心蛋白聚糖的代谢方面表现出一致的差异。值得注意的是，当软骨细胞在藻酸盐珠中培养时，PGs 的这种地形依赖性表型表达得以保留。在成年关节中，来自胫骨平台未被半月板覆盖的中央区域的软骨细胞，该区域在体内承受高机械负荷，与来自半月板覆盖区域的细胞相比，合成的聚集蛋白聚糖较少，但核心蛋白聚糖较多。当将新生绵羊关节相同 AC 区域的软骨细胞作为外植体培养时，未检测到聚集蛋白聚糖或核心蛋白聚糖代谢的地形差异。本研究结果结合现有文献，使我们提出，AC 的出生后机械负荷可选择软骨细胞克隆或诱导不同关节区域软骨细胞表型表达的持久调节。这种细胞变化可能导致合成赋予 AC 最适合抵抗不同关节区域可变机械应力特性的 PG 群体。本研究强调了在检查软骨细胞的 PG 代谢时使用相同关节区域软骨的重要性。进一步研究机械负荷、区域软骨细胞表型选择以及这些细胞对合成代谢和分解代谢因子的反应之间的关系，可能为骨关节炎中 AC 退变的局灶性本质提供重要见解。
