The inhibition of PLCγ1 protects chondrocytes against osteoarthritis, implicating its binding to Akt
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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
Bing Zhang, email: [email protected]
Chun Xia, email: [email protected]
Keywords: PLCγ1; Akt; chondroprotection; rat OA model; OA chondrocytes
Received: July 26, 2017 Accepted: November 17, 2017 Published: December 15, 2017
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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