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

Smruti Pushalkar, Xin Li, Zoya Bronislavovna Kurago, Lalitha V. Ramanathapuram, Satoko Matsumura, Kenneth E. Fleisher, Robert Glickman, Wenbo Yan, Yihong Li, Deepak Saxena

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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 (n=30); patients with periodontal disease without a history of BP therapy (Control, n=10), patients with periodontal disease having history of BP therapy but without ONJ (BP, n=5) and patients with BRONJ (BRONJ, n=15). Denaturing gradient gel electrophoresis of polymerase chain reaction (PCR)-amplified 16S rRNA 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.

Original languageEnglish (US)
Pages (from-to)219-226
Number of pages8
JournalInternational Journal of Oral Science
Volume6
Issue number4
DOIs
StatePublished - Dec 11 2014
Externally publishedYes

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Bisphosphonate-Associated Osteonecrosis of the Jaw
Microbiota
Diphosphonates
Innate Immunity
Periodontal Diseases
Jaw
I-kappa B Kinase
Secretory Leukocyte Peptidase Inhibitor
Cathepsin G
Myeloblastin
Polymerase Chain Reaction
Denaturing Gradient Gel Electrophoresis
Osteonecrosis
Biofilms
rRNA Genes
Peroxidase
Sequence Analysis
Interleukin-6
Up-Regulation
Down-Regulation

Keywords

  • bisphosphonates
  • denaturing gradient gel electrophoresis
  • host response
  • innate immunity
  • oral microbiota
  • osteonecrosis of the jaw

ASJC Scopus subject areas

  • Dentistry(all)

Cite this

Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw. / Pushalkar, Smruti; Li, Xin; Kurago, Zoya Bronislavovna; Ramanathapuram, Lalitha V.; Matsumura, Satoko; Fleisher, Kenneth E.; Glickman, Robert; Yan, Wenbo; Li, Yihong; Saxena, Deepak.

In: International Journal of Oral Science, Vol. 6, No. 4, 11.12.2014, p. 219-226.

Research output: Contribution to journalArticle

Pushalkar, S, Li, X, Kurago, ZB, Ramanathapuram, LV, Matsumura, S, Fleisher, KE, Glickman, R, Yan, W, Li, Y & Saxena, D 2014, 'Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw', International Journal of Oral Science, vol. 6, no. 4, pp. 219-226. https://doi.org/10.1038/ijos.2014.46
Pushalkar, Smruti ; Li, Xin ; Kurago, Zoya Bronislavovna ; Ramanathapuram, Lalitha V. ; Matsumura, Satoko ; Fleisher, Kenneth E. ; Glickman, Robert ; Yan, Wenbo ; Li, Yihong ; Saxena, Deepak. / Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw. In: International Journal of Oral Science. 2014 ; Vol. 6, No. 4. pp. 219-226.
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