Venn G, Billingham M E, Hardingham T E
Kennedy Institute of Rheumatology, Hammersmith, London, UK.
Arthritis Rheum. 1995 Apr;38(4):525-32. doi: 10.1002/art.1780380410.
To determine whether chondrocytes in early experimental osteoarthritic (OA) cartilage continue to show increased synthesis and turnover of proteoglycans (PGs) during explant culture. A comparison was also made between the responsiveness of experimental OA and control cartilage to interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) after 1 day and 3 days in culture.
OA was induced in mature animals by sectioning of the anterior cruciate ligament followed by 3 months of normal exercise. PG synthesis in the articular cartilage was determined by measuring 35S-sulfate incorporation during explant culture over 1-3 days. Inhibition of PG synthesis was also determined with various concentrations of IL-1 beta and TNF alpha after 1 and 3 days in culture. PGs extracted from the articular cartilage over 1-3 days in culture were examined by agarose-polyacrylamide gel electrophoresis.
Up to 24 hours after excision from the joint, PG synthesis was higher in experimental OA cartilage than in control cartilage. It was also less sensitive to inhibition by TNF alpha. These differences were no longer detected after 48-72 hours in culture. There were no changes in the relative proportions of aggrecan and decorin/biglycan extracted from and synthesized by control and experimental OA cartilage over the 3 days in culture.
Previous results indicated that PG synthesis and turnover in articular cartilage was increased for many months after induction of experimental OA. Our present results show that the enhanced rate of PG synthesis and turnover were evident in freshly explanted tissue, but the differences were lost over 3 days in culture. A decreased responsiveness to TNF alpha was also lost. The hypermetabolic activity of experimental OA chondrocytes was thus reversible and not a permanent change in chondrocyte phenotype.
确定早期实验性骨关节炎（OA）软骨中的软骨细胞在组织块培养期间蛋白聚糖（PGs）的合成和周转是否持续增加。还比较了实验性OA软骨和对照软骨在培养1天和3天后对白细胞介素-1β（IL-1β）和肿瘤坏死因子α（TNFα）的反应性。
通过切断前交叉韧带并随后进行3个月的正常运动在成熟动物中诱导OA。通过测量组织块培养1至3天期间35S-硫酸盐的掺入来确定关节软骨中PG的合成。在培养1天和3天后，还使用不同浓度的IL-1β和TNFα测定PG合成的抑制情况。通过琼脂糖-聚丙烯酰胺凝胶电泳检查在培养1至3天期间从关节软骨中提取的PG。
从关节切除后长达24小时，实验性OA软骨中的PG合成高于对照软骨。它对TNFα抑制的敏感性也较低。在培养48 - 72小时后不再检测到这些差异。在培养的3天内，从对照和实验性OA软骨中提取并由其合成的聚集蛋白聚糖和饰胶蛋白聚糖/双糖链蛋白聚糖的相对比例没有变化。
先前的结果表明，在实验性OA诱导后许多个月，关节软骨中的PG合成和周转增加。我们目前的结果表明，PG合成和周转的增强速率在新鲜组织块中很明显，但在培养3天后差异消失。对TNFα的反应性降低也消失了。因此，实验性OA软骨细胞的高代谢活性是可逆的，不是软骨细胞表型的永久性变化。
