Oncotarget

Research Papers:

The inhibition of PLCγ1 protects chondrocytes against osteoarthritis, implicating its binding to Akt

Heguo Cai, Ning Qu, Xiaolei Chen, Yang Zhou, Xinpeng Zheng, Bing Zhang _ and Chun Xia

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Oncotarget. 2018; 9:4461-4474. https://doi.org/10.18632/oncotarget.23286

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Abstract

Heguo Cai1,3,*, Ning Qu2,*, Xiaolei Chen1, Yang Zhou1, Xinpeng Zheng1, Bing Zhang2 and Chun Xia1

1Zhongshan Hospital, Xiamen University, Fujian 361004, China

2School of Medicine, Xiamen University, Fujian 361102, China

3The Third Hospital of Xiamen, Fujian, China, Fujian 361000, China

*These authors contributed equally to this work

Correspondence to:

Bing Zhang, email: cristal66@xmu.edu.cn

Chun Xia, email: chunxia@xmu.edu.cn

Keywords: PLCγ1; Akt; chondroprotection; rat OA model; OA chondrocytes

Received: July 26, 2017     Accepted: November 17, 2017     Published: December 15, 2017

ABSTRACT

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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