Nakase T, Miyaji T, Tomita T, Kaneko M, Kuriyama K, Myoui A, Sugamoto K, Ochi T, Yoshikawa H
Department of Orthopaedic Surgery, Osaka National Hospital, Osaka, Japan.
Osteoarthritis Cartilage. 2003 Apr;11(4):278-84. doi: 10.1016/s1063-4584(03)00004-9.
To examine the localization of bone morphogenetic protein (BMP)-2 mRNA and protein in human osteoarthritic (OA) articular cartilage and osteophyte.
Five normal, four growing and 14 OA human cartilage samples, graded histomorphologically by Mankin Score, were studied by in situ hybridization and immunohistochemistry for the expression of BMP-2.
BMP-2 mRNA was present in chondrocytes in neonatal growing articular cartilage, but was scarcely present in normal adult articular cartilage. In OA articular cartilage, BMP-2 mRNA and protein were detected in both clustering and individual chondrocytes in moderately or severely damaged OA cartilage. In moderately damaged OA cartilage, BMP-2 mRNA was localized in both upper and middle zone chondrocytes, but was not detected in deep layer chondrocytes. In severely damaged OA cartilage, cellular localization of BMP-2 mRNA was extended to the deep zone. In the area of osteophyte formation, BMP-2 mRNA was intensely localized in fibroblastic mesenchymal cells, fibrochondrocytes, chondrocytes and osteoblasts in newly formed osteophytic tissue. The pattern of BMP-2/4 immunolocalization was associated with that of mRNA localization.
BMP-2 mRNA and BMP-2/4 were detected in cells appearing in OA tissues. BMP-2 was localized in cells of degenerating cartilage as well as osteophytic tissue. Given the negative localization of BMP-2 in normal adult articular cartilage, BMP-2 might be involved in the regenerating and anabolic activities of OA cells, which respond to cartilage damage occurring in osteoarthritis.
研究骨形态发生蛋白(BMP)-2 mRNA和蛋白在人骨关节炎(OA)关节软骨和骨赘中的定位。
采用原位杂交和免疫组化方法,对5例正常、4例生长中及14例OA人软骨样本(根据Mankin评分进行组织形态学分级)中BMP-2的表达进行研究。
BMP-2 mRNA在新生儿生长中的关节软骨软骨细胞中存在,但在正常成人关节软骨中几乎不存在。在OA关节软骨中,在中度或重度损伤的OA软骨中的聚集和单个软骨细胞中均检测到BMP-2 mRNA和蛋白。在中度损伤的OA软骨中,BMP-2 mRNA定位于上层和中层软骨细胞,但在深层软骨细胞中未检测到。在重度损伤的OA软骨中,BMP-2 mRNA的细胞定位扩展到深层。在骨赘形成区域,BMP-2 mRNA强烈定位于新形成的骨赘组织中的成纤维细胞间充质细胞、纤维软骨细胞、软骨细胞和成骨细胞。BMP-2/4免疫定位模式与mRNA定位模式相关。
在OA组织中出现细胞中检测到BMP-2 mRNA和BMP-2/4。BMP-2定位于退变软骨细胞以及骨赘组织细胞中。鉴于BMP-2在正常成人关节软骨中的阴性定位,BMP-2可能参与OA细胞的再生和合成代谢活动,这些细胞对骨关节炎中发生的软骨损伤作出反应。