颗粒蛋白前体通过激活ERK1/2信号通路预防股骨头坏死
Progranulin Protects Against Osteonecrosis of the Femoral Head by Activating ERK1/2 Pathway.
作者信息
Han Yingguang, Si Meng, Zhao Yunpeng, Liu Yi, Cheng Kaiyuan, Zhang Yuedong, Jia Jialin, Li Jingkun, Nie Lin
机构信息
Department of Orthopaedic Surgery, Shandong University Qilu Hospital, No. 107, Wen Hua Xi Road, Jinan, Shandong, 250012, People's Republic of China.
Department of Orthopaedic Surgery, Taian Central Hospital, Taian, Shandong, 271000, China.
出版信息
Inflammation. 2017 Jun;40(3):946-955. doi: 10.1007/s10753-017-0539-z.
The aim of this study was to investigate progranulin (PGRN) expression and its effect in cartilage degradation and in the pathogenesis of osteonecrosis of the femoral head (ONFH). Cartilage specimens were obtained from ONFH and FNF patients and PGRN expression was analyzed by immunohistochemistry, western blot analysis, and RT-PCR. Peripheral blood PGRN level was detected by ELISA. Additionally, primary chondrocytes were cultured and treated with PGRN. Next, the expression of aggrecan and collagen II and the activation of ERK1/2 were detected. We observed that the expression of PGRN was significantly upregulated in ONFH patients' articular cartilage, and recombinant PGRN could promote expression of aggrecan and collagen II and the activation of ERK1/2. Collectively, PGRN can improve chondrocyte anabolism and perform a therapeutic role in the pathogenesis of ONFH. This study helps to elucidate the pathogenesis of ONFH and presents PGRN as a potential target for the treatment of ONFH.
本研究旨在探讨颗粒蛋白前体（PGRN）的表达及其在软骨降解和股骨头坏死（ONFH）发病机制中的作用。从ONFH患者和股骨颈骨折（FNF）患者获取软骨标本，通过免疫组织化学、蛋白质印迹分析和逆转录-聚合酶链反应（RT-PCR）分析PGRN表达。采用酶联免疫吸附测定（ELISA）检测外周血PGRN水平。此外，培养原代软骨细胞并用PGRN处理。接下来，检测聚集蛋白聚糖和Ⅱ型胶原的表达以及细胞外信号调节激酶1/2（ERK1/2）的激活情况。我们观察到，ONFH患者关节软骨中PGRN的表达显著上调，重组PGRN可促进聚集蛋白聚糖和Ⅱ型胶原的表达以及ERK1/2的激活。总体而言，PGRN可改善软骨细胞合成代谢，并在ONFH发病机制中发挥治疗作用。本研究有助于阐明ONFH的发病机制，并将PGRN作为ONFH治疗的潜在靶点。
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