Objective:Osteoradionecrosis of jaws(ORNJ)is considered to be one of the most devastating longterm complications of head and neck radiotherapy,which is still lack of ideal treatment.Recent literatures and our previous studies have shown that the excessive proliferation and secretion of extracellular matrix of myofibroblasts(MFB)played an important role in the radiation-induced fibrotic mechanism of ORNJ.MFB is an intermediate state cell which can transfer its phenotype stimulated by specific molecules such as BMP-2 or mechanical changes.This study was aimed to reveal the role of MFB phenotypic transformation in the pathogenesis of ORNJ,and to preliminarily explore the therapeutic effects of MFB phenotypic modulation by BMP-2 on ORNJ.Methods:Rabbits were divided into control group,low-dose(LD),middle-dose(MD),high-dose(HD)irradiation groups,and BMP-2 group.The time dependent and dose-related alteration of MFB,TGF-β1,Col Ⅰ and Col Ⅲ expression of the animal tissues were detected.MFB were cultured with tissue pieces harvested from the irradiated region of mandibles,and the expression of α-SMA,Col Ⅰ and Col Ⅲ were observed.The effects of BMP-2 on MFB were evaluated by the expression of α-SMA,Col Ⅰ and Col Ⅲ.BMSCs cultured from rabbits mandibles were irradiated and treated with BMP-2,and the expression of α-SMA,Col Ⅰ and Col Ⅲ were detected.Results:The extent of tissue damage,α-SMA positive cell number and staining intensity,and the expression level of TGF-β1,Col Ⅰ and Col Ⅲ were increased in the ORNJ tissues compared to the control group,and they increased with the radiation dose increasing,while decreased in BMP-2 group; α-SMA positive cell number and staining intensity,and the expression of Col Ⅰ and Col Ⅲ were increased while the expression of TGF-β1 was decreased over time.Compared to fibroblasts,MFB showed high-level expression of α-SMA,and the expression of Col Ⅰ and Col Ⅲ were increased.After treatment with BMP-2,MFB showed decreased expression of α-SMA,Col Ⅰ and Col Ⅲ.Being treated with BMP-2,the expression of α-SMA,Col Ⅰ and Col Ⅲ in irradiated BMSCs decreased significantly.Conclusion:The myofibroblasts phenotype transformation may play an important role in the pathogenesis of ORNJ and BMP-2 could regulate phenotypic of MFB,promote bone formation and reduce tissue fibrosis,which may have treatment effects on ORNJ and pave the way for a new and more effective therapy in the future.