RESUMO
Background: Osteoradionecrosis (ORN) is a serious complication of radiotherapy for head and neck cancer. There is currently a lack of data on the dynamic expression of genes related to bone remodeling during the development of mandibular ORN. This study aimed to establish an animal model of ORN in Sprague Dawley (SD) rats, detect the expression of genes related to bone metabolism, observe morphological changes, and clarify the mechanism of ORN. Methods: A total of 24 male SD rats in group 1 were randomly divided into four groups (n=6/group): group a, normal control; group b, simple tooth extraction; group c, simple radiation; and group d, radiation extraction group. The right mandible of rats in groups c and d was irradiated with a single dose of 35 Gy. The right mandibles were taken from each group for morphological observation 90 days after irradiation. SD rats in group 2 (n=144) were randomly divided into four groups (in similar fashion to group 1 but with groups a', b', c', and d'). Samples were collected at six time points after irradiation. Histopathological changes were observed, and Western blotting (WB) was used to analyze protein expression. Results: The formation of dead bone and pathological fracture was visible under micro-computed tomography (micro-CT), and tissue biopsy showed late fibrosis repair. In group d', osteogenesis and osteoclasis coexisted in the early irradiation stage. Vascular endothelial growth factor (VEGF) receptor expression was lower in groups c' and d' than in group a'. On day 45, runt-related transcription factor 2 (RUNX2) expression in group d' was lower than that in the other groups. The ratio of receptor activator of nuclear factor-κß ligand to osteoprotegerin (RANKL:OPG) differed significantly among groups b', c', and d' on the 45th day (d' > c' > b'). Conclusions: Radiation and vascular function damage resulted in the lower expression of VEGF. The first 15 days after radiation was mainly characterized by new bone formation. After 15 days, bone resorption increased. Tooth extraction trauma can aggravate the bone metabolism imbalance and promote ORN occurrence. These findings shed light on the mechanism of ORN.
RESUMO
OBJECTIVES: To investigate the relationship between polymorphisms of calcitonin-related peptide gene II (beta-calcitonin gene-related peptide (ßCGRP), CALCB) and serum CGRP levels in salivary adenoid cystic carcinoma. MATERIALS AND METHODS: Using the polymerase chain reaction (PCR) technique, the full-length amplification and genotype analysis of CALCB genes were performed in 39 patients with adenoid cystic carcinoma of salivary gland and 158 normal controls. The gene frequencies of major genotype of CALCB in adenoid cystic carcinoma of salivary gland and normal control group were analyzed. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate serum calcitonin gene-related peptide (CGRP) and its concentration of alpha and beta subtypes. RESULTS: Univariate logistic regression analysis showed that the CALCB rs2839222 T/T genotype was closely related to the occurrence of salivary adenoid cystic carcinoma, with a correlation coefficient of 3.89. CONCLUSIONS: The serum CGRP concentration in the salivary adenoid cystic carcinoma group was 1.56 times that of the normal control group. The αCGRP subtype was significant, which was 3.02 times that of the normal control. The polymorphism of ßCGRP gene is associated with genetic susceptibility to salivary adenoid cystic carcinoma, and serum CGRP and ßCGRP can be used as novel markers of salivary adenoid cystic carcinoma.