An elevated IL-17 level was correlated with altered M1 and M2 macrophage phenotypes in mucosal tissues bordering extraction socket of C57BL/6 mice with BRONJ-like lesions. Mice were intravenously given one dose of zoledronate (Zol) (125μg/kg) one week before tooth extraction followed by intravenous injection of Zol twice a week for two weeks. A, Dynamic changes in serum IL-17 levels of C57BL/6 mice within one week after tooth extraction. Data represent mean ± SEM (n=5 per group). **P<0.01. B, An elevated serum IL17 level was correlated with BRONJ-like lesion development. Ext (−), normal mice without tooth extraction; Ext control, mice with tooth extraction but without Zol treatment; Zol(+)BRONJ(−), mice with tooth extraction and Zol treatment but without BRONJ-like lesion development; Zol(+)BRONJ(+), mice with tooth extraction and Zol treatment developed BRONJ-like lesions. Data represent mean ± SEM (n=5 per group). *P<0.05, **P<0.01 as compared with Ext control. $$P < 0.01 as compared with Zol (+) BRONJ (−). C–F, Real-time PCR analysis showed increased expression of IL-17, iNOS mRNA but decreased expression of arginase-1 mRNA in soft socket tissues of Zol(+)BRONJ(+) mice as compared with those of Zol(+)BRONJ(−) mice. Data represent mean ± SEM (n=5 per group). *P<0.05, **P<0.01 as compared with Ext (+) control. $P < 0.05, $$P < 0.01 as compared with Zol (+) BRONJ (−). G and H, Immunofluorescence studies showed an increased number of CD11b+ iNOS+ M1 macrophages and a decreased number of CD11b+ Arginase-1+ (Arg-1) M2 macrophages (an increased M1/M2 ratio) in mucosal tissues bordering socket tissues of Zol(+)BRONJ(+) mice as compared with those of Zol(+)BRONJ(−) mice. Scale bars, 100 μm. Data represent mean ± SEM quantification of M1/M2 macrophages (multiple images, n=3 per group). **P<0.01 as compared with Ext control. $P < 0.05, $$P < 0.01 as compared with Zol (+) BRONJ (−).