Pfander D, Cramer T, Weseloh G, Pullig O, Schuppan D, Bauer M, Swoboda B
Division of Orthopedic Rheumatology, Department of Orthopedic Surgery, University of Erlangen-Nuernberg, Erlangen, Germany.
Osteoarthritis Cartilage. 1999 Nov;7(6):548-59. doi: 10.1053/joca.1999.0259.
Hepatocyte growth factor/scatter factor is a potent mitogen, morphogen and motogen for a variety of mainly epithelial cells. Hepatocyte growth factor is synthesized by mesenchymal cells and can be found in various tissues. The objective of this study was to investigate the expression and distribution patterns of this pleiotropic growth factor and its receptor, the product of the proto-oncogene c-met in normal and osteoarthritic human knee cartilage.
Five normal and 14 osteoarthritic human cartilage samples graded histomorphologically by Mankin Score, were studied by radioactive in-situ hybridization and immunohistochemistry for the expression of Hepatocyte growth factor and the c-met receptor.
Hepatocyte growth factor could be found by immunohistochemistry in the territorial matrix surrounding the chondrocytes of calcified cartilage and within the deep zone of normal cartilage. Chondrocytes of these cartilage zones showed also positive c-met receptor-staining. Moreover, a small number of chondrocytes in the superficial and intermediate zone showed c-met staining. In accordance with the increased hepatocyte growth factor staining of osteoarthritic cartilage, an enhanced expression of hepatocyte growth factor-RNA by chondrocytes of the deep zone as well as the deeper mid zone was observed. Contrary to normal cartilage, c-met was identified immunohistochemically in osteoarthritic chondrocytes of all cartilage zones.
These results indicate that hepatocyte growth factor seems to be acting in an autocrine/paracrine manner in normal and osteoarthritic cartilage. The ubiquitous presence of the HGF/HGF-receptor complex in osteoarthritic chondrocytes suggests that hepatocyte growth factor may contribute to the altered metabolism in osteoarthritic cartilage.
肝细胞生长因子/散射因子是多种主要上皮细胞的强效促有丝分裂剂、形态发生素和促运动因子。肝细胞生长因子由间充质细胞合成,可在多种组织中发现。本研究的目的是调查这种多效性生长因子及其受体(原癌基因c-met的产物)在正常和骨关节炎人类膝关节软骨中的表达和分布模式。
对5份正常和14份经曼金评分组织形态学分级的骨关节炎人类软骨样本,采用放射性原位杂交和免疫组织化学方法研究肝细胞生长因子和c-met受体的表达。
通过免疫组织化学可在钙化软骨软骨细胞周围的区域基质以及正常软骨的深层区域发现肝细胞生长因子。这些软骨区域的软骨细胞也显示出c-met受体染色阳性。此外,浅表层和中间层的少数软骨细胞显示出c-met染色。与骨关节炎软骨中肝细胞生长因子染色增加一致,观察到深层区域以及更深的中层区域的软骨细胞中肝细胞生长因子RNA表达增强。与正常软骨相反,在所有软骨区域的骨关节炎软骨细胞中通过免疫组织化学鉴定出c-met。
这些结果表明,肝细胞生长因子似乎在正常和骨关节炎软骨中以自分泌/旁分泌方式发挥作用。骨关节炎软骨细胞中HGF/HGF受体复合物的普遍存在表明,肝细胞生长因子可能导致骨关节炎软骨代谢改变。