Van Lent P L, Holthuysen A E, Van Rooijen N, Van De Putte L B, Van Den Berg W B
Department of Rheumatology, University Hospital Nijmegen, the Netherlands.
Ann Rheum Dis. 1998 Jul;57(7):408-13. doi: 10.1136/ard.57.7.408.
To investigate whether local removal of phagocytic synovial lining cells (SLCs) from the knee joint before onset of collagen type II arthritis has an effect on development of cartilage destruction.
Phagocytic SLCs were selectively depleted by a single injection of clodronate laden liposomes in the knee joint seven days before induction of collagen type II arthritis (CIA). Clodronate laden liposomes were given in one knee joint either alone or in combination with a short-term oral treatment of dexamethasone. Cartilage damage including proteoglycan depletion and chondrocyte death was measured in total knee joints sections stained with safranin-o or haematoxylin.
Local removal of phagocytic SLCs, seven days before arthritis onset, prevented cell influx for the larger part. Chondrocyte death was significantly decreased in the SLC depleted arthritic joint both at an early (6 days) and late (12 days) time point after CIA induction. However, depletion of proteoglycans from femoral and patellar cartilage layers was not prevented. If the mild acute inflammation caused by a single clodronate laden liposome injection in the left knee joint, was blocked by a short-term (on consecutive days 9, 8, 7, 6, 5 before CIA onset) oral treatment with dexamethasone, cell influx, but also proteoglycan depletion was almost completely blocked. In the contralateral control right knee joint prominent cell influx and severe cartilage damage was observed, indicating that there was no effect of dexamethasone anymore at the onset of CIA.
This study shows that removal of phagocytic lining cells before CIA induction, particularly in the presence of a short-term treatment with dexamethasone, decreases cartilage destruction.
研究在II型胶原性关节炎发病前局部清除膝关节吞噬性滑膜衬里细胞（SLCs）是否对软骨破坏的发展有影响。
在诱导II型胶原性关节炎（CIA）前7天，通过在膝关节单次注射载有氯膦酸盐的脂质体选择性清除吞噬性SLCs。载有氯膦酸盐的脂质体单独或与地塞米松短期口服治疗联合给予一个膝关节。在用番红O或苏木精染色的全膝关节切片中测量包括蛋白聚糖耗竭和软骨细胞死亡在内的软骨损伤。
关节炎发作前7天局部清除吞噬性SLCs在很大程度上阻止了细胞流入。在CIA诱导后的早期（6天）和晚期（12天）时间点，SLCs耗竭的关节炎关节中的软骨细胞死亡均显著减少。然而，股骨和髌软骨层的蛋白聚糖耗竭并未得到阻止。如果在左膝关节单次注射载有氯膦酸盐的脂质体引起的轻度急性炎症通过在CIA发作前连续几天（第9、8、7、6、5天）口服地塞米松来阻断，细胞流入以及蛋白聚糖耗竭几乎完全被阻断。在对侧对照右膝关节中观察到明显的细胞流入和严重的软骨损伤，表明在CIA发作时地塞米松不再有作用。
本研究表明，在诱导CIA之前清除吞噬性衬里细胞，特别是在短期使用地塞米松治疗的情况下，可减少软骨破坏。
