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oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw

International Journal of oral Science 2014年第4期6卷 219-226页

作者： Smruti Pushalkar Xin Li Zoya Kurago Lalitha V Ramanathapuram Satoko Matsumura Kenneth E Fleisher Robert Glickman Wenbo Yan Yihong Li Deepak Saxena Department of Basic Science and Craniofacial Biology New York University College of Dentistry Department of oral and Maxillofacial Pathology Radiology and Medicine New York University College of Dentistry Department of oral and Maxillofacial Surgery New York University College of Dentistry Department of Biology Nyack College

Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate（BP）-related osteonecrosis of the jaw（ONJ） or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bacteria, most of these difficult to cultivate and presents many clinical challenges. The purpose of this study was to characterize the bacterial diversity in BRONJ lesions and to determine host immune response. We examined tissue specimens from three cohorts（n530）; patients with periodontal disease without a history of BP therapy（Control, n510）, patients with periodontal disease having history of BP therapy but without ONJ（BP, n55） and patients with BRONJ（BRONJ, n515）. denaturing gradient gel electrophoresis of polymerase chain reaction（PCR）-amplified 16 S r RNA gene fragments revealed less bacterial diversity in BRONJ than BP and Control cohorts. Sequence analysis detected six phyla with predominant affiliation to Firmicutes in BRONJ（71.6%）, BP（70.3%） and Control（59.1%）. Significant differences（P,0.05） in genera were observed, between Control/BP, Control/BRONJ and BP/BRONJ cohorts. Enzyme-linked immunosorbent assay（ELISA）results indicated that the levels of myeloperoxidase were significantly lower, whereas interleukin-6 and tumor necrosis factor-alpha levels were moderately elevated in BRONJ patients as compared to Controls. PCR array showed significant changes in BRONJ patients with downregulation of host genes, such as nucleotide-binding oligomerization domain containing protein 2, and cathepsin G, the key modulators for antibacterial response and upregulation of secretory leukocyte protease inhibitor, proteinase 3 and conserved helix–loop–helix ubiquitous kinase. The results suggest that colonization of unique bacterial communities coupled with deficient innate immune response is likely to impact the pathogenesis of ONJ.

关键词： bisphosphonates denaturing gradient gel electrophoresis host response innate immunity oral microbiota osteonecrosis of the jaw

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