Effects Of VWF Level On Proliferation And Migration Of Osteosarcoma Cells And Blood Hypercoagulability After Major Orthopedics Operation

Part ? Effect of inhibition of v WF on proliferation and migration of osteosarcoma cellsBackground: Von Willebrand factor(vWF)is a major procoagulant molecule that was shown to differentiate between metastatic and primary osteosarcoma(OS)tissues and associated with increased metastasis.However,its functional role in osteosarcoma progression has yet been unclear.Objectives: The aim of this study was to characterize the functional role of v WF in osteosarcoma progression and to examine the existence of mi RNA-24/v WF axis in the oncogenesis and progression of osteosarcoma.Methods:The expression profile of vWF and mi RNA-24 in human osteosarcoma tissues and cell lines was characterized using immunofluorescence labelling and q RT-PCR analysis.The interaction between mi RNA-24 and v WF was identified by dual luciferase reporter assay.The effects of v WF and mi RNA-24 on osteosarcoma cells were assessed by cell proliferation,colony formation and migration.The clinical significance of mi RNA-24 in osteosarcoma patients was analyzed using Kaplan-Meier analyses and Pearson's chi-squared test.Results:Here we reported that the expression of vWF was significantly increased,but mi RNA-24 was significantly decreased in osteosarcoma tissues and cell lines SAOS-2,MG-63,143 B,U2OS,HOS.v WF was further validated as the target of mi RNA-24 in MG-63 cells.Mi RNA-24 obviously suppressed the proliferation and migration of MG-63 cells.However,the metastasis-inhibiting activity of mi RNA-24 was predominantly attenuated by overexpressing v WF.Clinically,low mi RNA-24 expression in human osteosarcoma tissues was significantly associated with tumor metastasis and predicted a poor survival in osteosarcoma patients.Conclusion:This work demonstrated that v WF functioned as a novel protooncogene and served as an important player in mi RNA-24 controlling cell metastasis in osteosarcoma progression.Targeting v WF therefore promises to be an effective biological target for osteosarcoma treatment.Part ? Relationship between changes of v WF and ADAMTS13 and blood hypercoagulability after joint replacementBackground: von Willebrand factor(vWF)is a carrier protein for factor VIII.vWF can bind the extracellular matrix(ECM)and platelets.v WF can also promote platelet adhesion and aggregation.ADAMTS13 can cleave von Willebrand factor in the central A2 domain of v WF to decrease its activity.ADAMTS13 and v WF level correlate with thrombosis risk and inversely with bleeding risk.Objectives: The aim of this study was to observe the changes of vWF and ADAMTS13 in blood of patients after joint replacement,and to further investigate the relationship between these changes and the blood coagulation status.Methods: We observed 93 patients underwent total hip arthroplasty(THA)or total knee arthroplasty(TKA).Blood samples were taken preoperatively and on postoperative days(PODs)1,2,3,5,and 7.Plasma ADAMTS13 antigen was determined with western blotting.The proteolytic activity was validated with the FRETS-VWF73 assay.v WF:Ag and v WF:RCo activity were measured by an enzyme-linked immunoabsorbent assay(ELISA).Prothrombin time(PT),thrombin time(TT),activated partial thromboplastin time(APTT),antithrombin III,plasma fibrinogen and D-dimer were measured on STA-R fully automated coagulation analyzer with corresponding reagents.Results: The levels of v WF antigen and activity in the patient increased from POD 1.In contrast,ADAMTS13 antigen and activity in the patients decreased significantly.Starting on POD 1,fibrinogen and D-dimer increased.No significant changes were observed for PT,APTT and TT.Conclusion: ADAMTS13 and vWF level showed a marked association with thrombosis risk.The level of ADAMTS13 and v WF may be potentially useful markers inpredicting thrombotic complications following arthroplasty,and inhibit the activity of vWF would be a new prophylaxis to reduce postoperative DVT and PE.