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晚期糖基化终产物表达与创伤后骨关节炎大鼠模型关节软骨矿化进展的相关性。

Latexin expression correlated with mineralization of articular cartilage during progression of post-traumatic osteoarthritis in a rat model.

机构信息

Department of Infectomic and Molecular Pathogenesis, Center for Research and Advanced Studies of the Polytechnic National Institute (CINVESTAV-IPN), Mexico City, Mexico.

Department of Physics, Center for Research and Advanced Studies of the Polytechnic National Institute (CINVESTAV-IPN), Mexico City, Mexico.

出版信息

Histol Histopathol. 2020 Mar;35(3):269-278. doi: 10.14670/HH-18-151. Epub 2019 Jul 17.

Abstract

As latexin has been linked with chondrocyte hypertrophic differentiation it is possible that this protein may also be involved in the mineralization of cartilage in OA. Therefore, we correlated latexin expression with the mineralization marker, alkaline phosphatase and determined the mineral deposition in the articular cartilage by analyzing the Ca/P ratio and the collagen fibrils pattern, during the progression of post-traumatic OA in a rat model. OA was induced by medial meniscectomy and post-surgery exercise for 5, 10, 20 and 45 days. Protein expression in articular cartilage was evaluated by immunofluorescence, histochemistry and Western blot. Minerals and structure of collagen fibrils in the superficial zone of cartilage were analyzed by energy dispersive X-ray spectroscopy (EDX) and atomic force microscopy (AFM) respectively. Protein expression analysis showed time-dependent up-regulation of latexin during OA progression. In the cartilage, latexin expression correlated with the expression and activity of alkaline phosphatase. EDX of the superficial zone of cartilage showed a Ca/P ratio closer to theoretical values for basic calcium phosphate minerals. The presence of minerals was also analyzed indirectly with AFM, as the collagen fibril pattern was less evident in the mineralized tissue. Latexin is expressed in articular cartilage from the early stages of post-traumatic OA; however, minerals were detected after latexin expression was up-regulated, indicating that its activity precedes and remains during the pathological mineralization of cartilage. Thus, our results contribute to the identification of molecules involved in the mineralization of articular chondrocytes.

摘要

由于 latxin 与软骨细胞的肥大分化有关,因此它也可能参与 OA 中软骨的矿化。因此,我们通过分析创伤后 OA 大鼠模型中软骨的碱性磷酸酶(一种矿化标志物)和 Ca/P 比值以及胶原纤维模式,来确定 latxin 表达与软骨矿化的相关性。OA 是通过内侧半月板切除术和术后 5、10、20 和 45 天的运动来诱导的。通过免疫荧光、组织化学和 Western blot 评估关节软骨中的蛋白表达。通过能量色散 X 射线光谱(EDX)和原子力显微镜(AFM)分别分析软骨表层的矿物质和胶原纤维结构。蛋白表达分析显示,在 OA 进展过程中,latxin 的表达呈时间依赖性上调。在软骨中,latxin 的表达与碱性磷酸酶的表达和活性相关。软骨表层的 EDX 显示 Ca/P 比值更接近磷酸钙矿物质的理论值。矿物质的存在也可以通过 AFM 间接分析,因为矿化组织中的胶原纤维模式不太明显。Latxin 在创伤后 OA 的早期阶段就表达于关节软骨中;然而,在 latxin 表达上调后才检测到矿物质,这表明其活性先于并贯穿于软骨的病理性矿化过程。因此,我们的结果有助于鉴定参与关节软骨矿化的分子。

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