Reversing Effects Of Zoledronic Acid On MC3T3-E1 And RAW264.7 Cells By Pentoxifylline

Objective:To investigate the mechanism of pentoxifylline(PTX)on MC3T3-E1 cell and RAW264.7 cell,and to provide a theoretical basis for the clinical treatment of Meditation-related osteonecrosis of the jaw(MRONJ).Methods:Mouse embryonic osteogenic precursors cells MC3T3-E1 and Mouse mononuclear macrophage leukemic cells RAW264.7 were treated with 3μg/mL Zoledronic acid(ZOL)and 1μg/mL Sodium pyrophosphate(Na4P2O710·H2O,NP)respectively,and treatment with pentoxifylline,cells proliferation was detected by CCK-8,cells cycle and apoptosis were detected by flow cytometry,cells migration was detected by the scratch test,osteoblast differentiation was detected by Alizarin red staining after osteoblast induction of MC3T3-E1,after the osteoclast induced differentiation of RAW264.7 with RANKL factor,the osteoclast differentiation of RAW264.7 was detected by TRAP staining.And the expressions of TGF-β1,Smad4,RANKL,RANK and OPG were detected by qPCR and Western blotting.Results:Pentoxifylline inhibited the apoptosis of MC3T3-E1 while promoted the apoptosis of RAW264.7(P<0.05).At 48h,zoledronic acid significantly inhibited the migration of MC3T3-E1 and RAW264.7 cells.Combined with pentoxifylline,zoledronic acid-induced migration inhibition was improved(P<0.05),while sodium pyrophosphate inhibits the mineralization of MC3T3-E1.Pentoxifylline decreased the expression of TGF-β1 in two cells.Pentoxifylline,zoledronic acid and sodium pyrophosphate promote the expression of OPG in MC3T3-E1.While zoledronic acid decreased the RANK protein expression,zoledronic acid combined with pentoxifylline improved this situation.Conclusions:Pentoxifylline reverse the promotion or inhibition effects of zoledronic acid on two cells.Sodium pyrophosphate inhibits the mineralization of MC3T3-E1.