Section of Orthopedic Surgery, Division of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Cell Tissue Res. 2011 May;344(2):321-32. doi: 10.1007/s00441-011-1154-1. Epub 2011 Apr 12.
Bone morphogenetic protein-7 (BMP-7) regulates cartilage metabolism and promotes matrix synthesis. However, the effect of BMP-7 on inflammatory arthritis remains unknown. We investigated the effect and mechanism of exogenous BMP-7 on cartilage and synovium in vivo in rat zymosan-induced arthritis. Zymosan was injected into the left knees of Wistar rats. Phosphate-buffered saline or BMP-7 at 10, 100, or 1000 ng per joint was injected into the left knee every 2 days. Normal joints acted as normal controls. The knee joints were analyzed histologically and immunohistologically at 14 days. Joint swelling was evaluated by measuring the transverse diameter of the knee joints. Synovial lysates were collected, and the concentrations of interleukin-1β (IL-1β), IL-6, and IL-10 were measured by enzyme-linked immunosorbent assay. Intra-articular injection of zymosan resulted in acute inflammation and was followed by cartilage degeneration. Local administrations of BMP-7 inhibited this loss of cartilage matrix in a dose-dependent manner. Immunohistochemical analysis demonstrated enhanced type II collagen levels in cartilage and enhanced BMP-7 levels in cartilage and synovium after exogenous BMP-7 treatment. Joint swelling and cell infiltration into synovium were significantly reduced by BMP-7 injections. Administration of BMP-7 decreased IL-1β production significantly and increased IL-10 production in the synovium. Thus, intra-articular injections of BMP-7 had a protective effect on cartilage degeneration in the inflammatory arthritis model by enhancing levels of BMP-7 in cartilage and suppressing the production of IL-1β in synovium.
骨形态发生蛋白 7（BMP-7）调节软骨代谢并促进基质合成。然而，BMP-7 对炎性关节炎的影响尚不清楚。我们研究了外源性 BMP-7 在佐剂型关节炎大鼠体内对软骨和滑膜的作用及其机制。将酵母聚糖注入 Wistar 大鼠的左膝关节。每隔 2 天向大鼠左膝关节注射磷酸盐缓冲液或 10、100 或 1000ng/关节的 BMP-7。正常关节作为正常对照。14 天时，对膝关节进行组织学和免疫组织化学分析。通过测量膝关节的横径评估关节肿胀。收集滑膜裂解物，并通过酶联免疫吸附试验测量白细胞介素-1β（IL-1β）、IL-6 和 IL-10 的浓度。关节内注射酵母聚糖导致急性炎症，随后发生软骨退化。BMP-7 的局部给药以剂量依赖性方式抑制这种软骨基质的丧失。免疫组织化学分析表明，外源性 BMP-7 处理后软骨中 II 型胶原水平升高，软骨和滑膜中 BMP-7 水平升高。BMP-7 注射显著减少了关节肿胀和滑膜细胞浸润。BMP-7 给药显著降低了滑膜中 IL-1β 的产生，并增加了滑膜中 IL-10 的产生。因此，关节内注射 BMP-7 通过增强软骨中 BMP-7 的水平并抑制滑膜中 IL-1β 的产生，对炎性关节炎模型中的软骨退化具有保护作用。
