4.7 Article

Commensal oral microbiota induces osteoimmunomodulatory effects separate from systemic microbiome in mice

期刊

JCI INSIGHT
卷 7, 期 4, 页码 -

出版社

AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.140738

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资金

  1. American Society for Bone and Mineral Research
  2. NIH [K08DE025337, R01DE021423, T32DE017551, R25DE022677, P30GM103331, P20GM130457, P30DK123704, P20GM121342, R01DE029637, R01AG067510]
  3. MUSC DDRCC Advanced Imaging Core
  4. MUSC CDLD Animal Models Core

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Commensal oral microbiota has distinct osteoimmunomodulatory effects separate from the systemic microbiome, leading to enhanced pro-osteoclastic actions in alveolar bone through increased TLR signaling and Th17 cells. These effects are limited to the bone marrow of alveolar bone and not long bone.
Commensal microbes critically regulate skeletal homeostasis, yet the impact of specific microbiota communities on osteoimmune response mechanisms is unknown. To discern osteoimmunomodulatory effects imparted by the commensal oral microbiota that are distinct from the systemic microbiota, osteoimmunology studies were performed in both alveolar bone and nonoral skeletal sites of specific pathogen-free (SPF) versus germ-free (GF) mice and SPF mice subjected to saline versus chlorhexidine oral rinses. SPF versus GF mice had reduced cortical/ trabecular bone and an enhanced pro-osteoclastic phenotype in alveolar bone. TLR signaling and Th17 cells that have known pro-osteoclastic actions were increased in alveolar BM, but not long BM, of SPF versus GF mice. MHC II antigen presentation genes and activated DCs and CD4(+) T cells were elevated in alveolar BM, but not long BM, of SPF versus GF mice. These findings were substantiated by in vitro allostimulation studies demonstrating increased activated DCs derived from alveolar BM, but not long BM, of SPF versus GF mice. Chlorhexidine antiseptic rinse depleted the oral, but not gut, bacteriome in SPF mice. Findings from saline-versus chlorhexidine-treated SPF mice corroborated outcomes from SPF versus GF mice, which reveals that the commensal oral microbiota imparts osteoimmunomodulatory effects separate from the systemic microbiome.

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