The Role Of Hmgb1-Related Inflammation Signals In Bronj

BRONJ causes prolonged inflammation, resulting in delayed wound healing. High mobility group box-1 (HMGB1) is secreted into the extracellular milieu in response to stimuli, which mediates various inflammatory diseases and affects wound healing. The aim of this study is to investigate the role of HMGB1-related inflammation in jaw necrosis with zoledronic acid administration, and to lay a foundation for further exploration of the pathogenesis of BRONJ Twenty-four female SD mice were randomized to divided into two groups: the zoledronic acid group, which were injected zoledronate(0.2mg/kg/week) through the tail vein; and the control group, which were injected the same equal saline solution for 12 consecutive weeks. The mice were initially anesthetized with pentobarbital (50 mg/kg body weight); the left first maxillary molar was extracted as the test site. The maxillary tissues were collected 3 ,7 days,2 weeks and 4 weeks after the tooth extraction. Detecting the expression of HMGB1-related inflammation through HE staining,q-PCR and Immunofluorescence staining. The tooth-extracted sockets in ZA group did not heal, and exposed necrotic bone. Histopathological examination revealed that osteoclasts were inhibited and necrotic bone was formed. The q-PCR and Immunofluorescence staining indicated that the expressions of HMGB1, RAGE, and IL-1β were significantly increased in ZA group. HMGB1-related inflammatory signals and related inflammatory factors significantly increase in the tooth-extracted sockets after bisphosphonate administration, further inducing inflammatory responses and leading to Bisphosphonate-Related Osteonecrosis of the Jaw.