ABSTRACT

Objective: Refractory infection is an important factor affecting the progression of medication-related osteonecrosis of the jaw (MRONJ) from clinical stage I to stage II/III. The aim of this study was to explore the distribution of bacteria and their association with the inflammatory pathway of stage II/III MRONJ.

Materials and Methods: Nine specimens of fresh inflammation tissue, located next to the necrotic bone or sequestrum, were collected from MRONJ patients. Nine specimens from normal oral mucosa were collected from healthy patients. The 16S rRNA gene sequencing method was used to determine the distribution characteristics of the bacterial colony. The protein microarray analysis was used to detect the expression of inflammatory cytokines.

Results: The average relative abundance of Bacteroidetes, Spirochaetes, Synergistetes, and Tenericutes was higher, while Proteobacteria and Actinobacteria were lower in the MRONJ group. Most pro-inflammatory cytokines were up-regulated in the MRONJ group; yet, only IFNγ, TNFα, and IL8 showed statistical differences (P < 0.05). Porphyromonas and Treponema were positively correlated with IL8, and Mogibacterium was positively correlated with IFNγ and TNFα.

Conclusions: IL8/IFNγ/TNFα pro-inflammatory effect caused by Porphyromonas, Treponema, and Mogibacterium may be the leading cause of advancing MRONJ and thus may be used as a new target for infection control.

摘要

目的：难治性感染是影响药物相关的颌骨坏死（MRONJ）从临床I期到II / III期发展的重要因素。这项研究的目的是探讨细菌的分布及其与II / III期MRONJ炎症途径的关系。

材料和方法：从MRONJ患者中收集9个新鲜的炎症组织标本，位于坏死骨或死骨附近。从健康患者中收集了九份来自正常口腔粘膜的标本。16S rRNA基因测序方法用于确定细菌菌落的分布特征。蛋白质微阵列分析用于检测炎性细胞因子的表达。

结果：平均相对丰度拟杆菌，螺旋体，Synergistetes和Tenericutes较高，而变形菌和放线菌是在MRONJ组低。MRONJ组大多数促炎细胞因子上调；但是，只有IFNγ，TNFα和IL8表现出统计学差异（P <0.05）。卟啉单胞菌和梅毒螺旋体与IL8呈正相关，而动杆菌属与IFNγ和TNFα呈正相关。

结论：卟啉菌，梅毒螺旋体和杆菌引起的IL8 /IFNγ/TNFα促炎作用可能是促进MRONJ进展的主要原因，因此可以作为感染控制的新目标。