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- W3115124466 abstract "Abstract Previous studies identified the involvement of phosphoinositide‐specific phospholipase C (PLC) γ1 in some events of chondrocytes. This study aims to investigate whether and how PLCγ1 modulates autophagy to execute its role in osteoarthritis (OA) progression. Rat normal or human OA chondrocytes were pretreated with IL‐1β for mimicking or sustaining OA pathological condition. Using Western blotting, immunoprecipitation, qPCR, immunofluorescence and Dimethylmethylene blue assays, and ELISA and transmission electron microscope techniques, we found that PLCγ1 inhibitor U73122 enhanced Collagen II, Aggrecan and GAG levels, accompanied with increased LC3B‐II/I ratio and decreased P62 expression level, whereas autophagy inhibitor Chloroquine partially diminished its effect. Meanwhile, U73122 dissociated Beclin1 from Beclin1‐IP3R‐Bcl‐2 complex and blocked mTOR/ULK1 axis, in which the crosstalk between PLCγ1, AMPK, Erk and Akt were involved. Additionally, by haematoxylin and eosin, Safranin O/Fast green, and immunohistochemistry staining, we observed that intra‐articular injection of Ad‐shPLCγ1‐1/2 significantly enhanced Collagen and Aggrecan levels, accompanied with increased LC3B and decreased P62 levels in a rat OA model induced by anterior cruciate ligament transection and medial meniscus resection. Consequently, PLCγ1 inhibition‐driven autophagy conferred cartilage protection against OA through promoting ECM synthesis in OA chondrocytes in vivo and in vitro, involving the crosstalk between PLCγ1, AMPK, Erk and Akt." @default.
- W3115124466 created "2021-01-05" @default.
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- W3115124466 date "2020-12-28" @default.
- W3115124466 modified "2023-09-23" @default.
- W3115124466 title "PLCγ1 inhibition‐driven autophagy of IL‐1β‐treated chondrocyte confers cartilage protection against osteoarthritis, involving AMPK, Erk and Akt" @default.
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- W3115124466 doi "https://doi.org/10.1111/jcmm.16245" @default.
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