The inhibition of PLCγ1 protects chondrocytes against osteoarthritis, implicating its binding to Akt.
The inhibition of PLCγ1 protects chondrocytes against osteoarthritis, implicating its binding to Akt.
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PLCγ1 的抑制可保护软骨细胞免受骨关节炎的影响，这表明它与 Akt 结合。
DOI：
10.18632/oncotarget.23286
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发表时间：
2018-01-12
期刊：
影响因子：
--
通讯作者：
Xia C
中科院分区：
文献类型：
--
作者：
Cai H;Qu N;Chen X;Zhou Y;Zheng X;Zhang B;Xia C
以往的研究已发现磷脂酰肌醇特异性磷脂酶γ1（PLCγ1）和蛋白激酶B（PKB/Akt）参与骨关节炎（OA）的发病，但尚未确定它们作为OA治疗靶点的可能性。本研究通过关节腔内注射PLCγ或Akt抑制剂，建立大鼠前交叉韧带切断加内侧半月板切除的OA模型，采用组织病理学方法观察关节软骨细胞和基质的构筑，采用免疫组化方法检测关节软骨中Aggrecan、Col 2、PLCγ1和Akt的表达。用Akt或PLCγ抑制剂处理OA模型大鼠软骨细胞，并转染PLCγ1或PLCγ1-Akt表达载体，Western blotting检测Aggrecan、Col 2、PLCγ1、p-PLCγ1、Akt和p-Akt表达水平。用免疫共沉淀法检测PLCγ1与Akt的结合。这些结果表明，PLCγ抑制保护软骨细胞免受OA，但Akt抑制没有显着加剧OA的进展。PLCγ1与Akt之间存在相互拮抗和结合作用，并可通过其磷酸化水平进行调节。因此，数据显示PLCγ1的抑制可能为OA治疗提供有吸引力的治疗靶点，暗示其与Akt的结合。
Previous studies have addressed the involvement of phosphoinositide-specifc phospholipase γ1 (PLCγ1) and protein kinase B (PKB/Akt) in osteoarthritis (OA) pathogenesis, but it is not ascertained the possibility of them to be potential targets for OA therapy. Here, through local intra-articular injection of PLCγ or Akt inhibitor in a rat OA model induced by anterior cruciate ligament transaction plus medial meniscus resection, the architecture of chondrocyte and matrix organization of articular cartilage were observed using histopathological assays and Aggrecan, Col2, PLCγ1, and Akt levels were detected using immunohistochemistry assays. By treatment of Akt or PLCγ inhibitor and transfection of different PLCγ1- or Akt-expressing vectors in rat OA model chondrocytes, Aggrecan, Col2, PLCγ1, p-PLCγ1, Akt, and p-Akt levels were detected using western blotting analysis. The binding between PLCγ1 and Akt was assessed with co-immunoprecipitation assays in human OA chondrocytes. These results showed that PLCγ inhibition protected chondrocytes against OA, but Akt inhibition did not dramatically aggravate OA progression. There were mutual antagonism and binding between PLCγ1 and Akt that could be regulated by their phosphorylation levels. Consequently, the data reveal that the inhibition of PLCγ1 may provide an attractive therapeutic target for OA therapy, implicating its binding to Akt.
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