Disruption Of Phosphoinositide-specific Phospholipases Cγ1Contributes To Extracellular Matric Synthesis Of Human Osteoarthritis Chondrocytes

Backgrounds/Aims: To determine the role of phophoinositide-specificphospholipases Cγ1(PLCγ1) in human osteoarthritis (OA) progression.Methods:Acqure chondrocyte from knee articular of human OA patient and thenomal person respectively.Comparing the expression level(by western blotting) ofplcγ1.P-Plcγ1and downstreaming protein in OA chondrocyte and in control.Using theIHC to detecting the level of plcγ1between the OA chondrocyte and the control.Thencultured OA chondrocytes were treated with U73122(inhibitor of plcγ1),and thendetected some signaling molescules involved in ECM metabolism.In order todecreased the level of plcγ1,siRNA targets plcγ1were designed and synthesised,andthen be transfected into chondrocytes by lipo2000.At last,OA chondrocytes weredealed with DAG inhibitor and IP3inhibitor,and then the downstreaming signalingprotein were detected.Results:PLCγ1had a higher expression in OA cartilage and chondrocyte,comparedwith normal cartilage and chondrocyte,and the disruption of PLCγ1by itsinhibitor,U73122,and siRNA promoted the extracellular matrix(ECM) synthesis ofhuman OA chondrocytes. Furthermore,the PLCγ1/IP3/Ca2+/Camk signalingaxis,,which triggered mTOR/P70S6K/S6pathway, was dominated inPLCγ1-depended ECM synthesis.Conclusion: PLC-γ1is involved in ECM synthesis of OA chondrocytes,and thedisruption of PLCγ1contributes to ECM synthesis of human OA chondrocytes.PLCγ1may serve as a thetapeutic target for the prevention of OA.PLC-γ1.