Guo Jing, Zhang Wenli, Li Qijia, Gan Hongquan, Wang Zhiqiang
Medical Experimental and Research Center, Hebei United University, Tangshan Hebei 063000, PR China.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2011 Aug;25(8):992-7.
It is reported that transforming growth factor beta1 (TGF-beta1) has the protective effects on the articular cartilage in osteoarthritis (OA). To investigate the significance of the expressions of matrix metalloproteinase 9 (MMP-9), TGF-beta1 mRNA and corresponding proteins in OA.
The specimens of articular cartilage and synovium were collected from voluntary donators, including 60 cases of OA (experimental group) and 20 cases of traumatic amputation, cruciate ligament rupture, discoid cartilage injury, and menisci injury (normal control group). The pathological changes were observed by HE staining. MMP-9 and TGF-beta1 protein expressions were detected by immunohistochemical technique, and the mRNA expressions of MMP-9 and TGF-beta1 were detected through in situ hybridization technique; and their correlation was analysed.
HE staining showed: shrinkage, necrosis, and irregular arrange of the articular chondrocytes, extracellular matrix fracture, hypertrophy and hyperplasia synovium, infiltration of lymphoid and mononuclear cells and proliferation of many small blood vessels in the experimental group; regular arrangement of the articular chondrocytes, the homogeneously staining matrix, and synovial tissue without chronic inflammation and significant proliferation in the normal control group. The mRNA and protein expressions of MMP-9 and TGF-beta1 were positive in 2 groups. The positive-stained cells included chondrocytes, synovial lining cells, and vascular endothelial cells, fibroblasts, and inflammatory infiltrated cells in subsynovial layer. The expressions of mRNA and corresponding protein of MMP-9 and TGF-beta1 in the experimental group were significantly higher than those in the normal control group (P < 0.01). There was a positive correlation between MMP-9 mRNA and protein expression (r = 0.924, P = 0.000), and between TGF-beta1 mRNA and protein expression (r = 0.941, P = 0.000) in the experimental group. There was a negative correlation between the expression of MMP-9 protein and TGF-beta1 protein (r = 0.762, P = 0.000), and between the expression of MMP-9 mRNA and TGF-beta1 mRNA (r = -0.681, P = 0.000) in the experimental group.
The higher expression of TGF-beta1 can protect articular cartilage by down-regulating the expression of MMP-9 of chondrocytes and synoviocytes in OA, which may delay the biological behavior of OA such as occurrence and progress, etc.
据报道，转化生长因子β1（TGF-β1）对骨关节炎（OA）的关节软骨具有保护作用。探讨基质金属蛋白酶9（MMP-9）、TGF-β1 mRNA及相应蛋白在OA中的表达意义。
从自愿捐献者处采集关节软骨和滑膜标本，其中OA患者60例（实验组），创伤截肢、交叉韧带断裂、盘状软骨损伤及半月板损伤患者20例（正常对照组）。采用HE染色观察病理变化。采用免疫组化技术检测MMP-9和TGF-β1蛋白表达，采用原位杂交技术检测MMP-9和TGF-β1 mRNA表达，并分析其相关性。
HE染色显示：实验组关节软骨细胞皱缩、坏死、排列不规则，细胞外基质断裂，滑膜肥厚增生，淋巴细胞和单核细胞浸润，小血管增生；正常对照组关节软骨细胞排列规则，基质染色均匀，滑膜组织无慢性炎症及明显增生。两组MMP-9和TGF-β1的mRNA及蛋白表达均为阳性。阳性染色细胞包括软骨细胞、滑膜衬里细胞、血管内皮细胞、成纤维细胞及滑膜下层炎症浸润细胞。实验组MMP-9和TGF-β1的mRNA及相应蛋白表达均显著高于正常对照组（P<0.01）。实验组MMP-9 mRNA与蛋白表达呈正相关（r=0.924，P=0.000），TGF-β1 mRNA与蛋白表达呈正相关（r=0.941，P=0.000）。实验组MMP-9蛋白与TGF-β1蛋白表达呈负相关（r=0.762，P=0.000），MMP-9 mRNA与TGF-β1 mRNA表达呈负相关（r=-0.681，P=0.000）。
TGF-β1的高表达可通过下调OA中软骨细胞和滑膜细胞MMP-9的表达来保护关节软骨，这可能延缓OA的发生、发展等生物学行为。
