title: A role of oral bacteria in bisphosphonate-induced osteonecrosis of the jaw.
abstract: No consensus has yet been reached to associate oral bacteria conclusively with the etio-pathogenesis of bisphosphonate-induced osteonecrosis of the jaw (BONJ). Therefore, the present study examined the effects of oral bacteria on the development of BONJ-like lesions in a mouse model. In the pamidronate (Pam)-treated mice, but not control non-drug-treated mice, tooth extraction followed by oral infection with Fusobacterium nucleatum caused BONJ-like lesions and delayed epithelial healing, both of which were completely suppressed by a broad-spectrum antibiotic cocktail. Furthermore, in both in vitro and in vivo experiments, the combination of Pam and Fusobacterium nucleatum caused the death of gingival fibroblasts (GFs) and down-regulated their production of keratinocyte growth factor (KGF), which induces epithelial cell growth and migration. Therefore, in periodontal tissues pre-exposed to bisphosphonate, bacterial infection at tooth extraction sites caused diminished KGF expression in GFs, leading to a delay in the epithelial wound-healing process that was mitigated by antibiotics.
authors.affiliation: Department of Immunology, The Forsyth Institute, 245 1 St., Cambridge, MA 02142, USA.
authors.forename: H
authors.initials: H
authors.lastname: Mawardi
authors.forename: G
authors.initials: G
authors.lastname: Giro
authors.forename: M
authors.initials: M
authors.lastname: Kajiya
authors.forename: K
authors.initials: K
authors.lastname: Ohta
authors.forename: S
authors.initials: S
authors.lastname: Almazrooa
authors.forename: E
authors.initials: E
authors.lastname: Alshwaimi
authors.forename: S-B
authors.initials: SB
authors.lastname: Woo
authors.forename: I
authors.initials: I
authors.lastname: Nishimura
authors.forename: T
authors.initials: T
authors.lastname: Kawai
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017209:Apoptosis; D050071:Bone Density Conservation Agents / Q000009:adverse effects; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D004164:Diphosphonates / Q000009:adverse effects; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology; D016967:Fusobacterium nucleatum / Q000472:pathogenicity*; D005881:Gingiva / Q000166:cytology / Q000382:microbiology; D007571:Jaw Diseases / Q000139:chemically induced / Q000382:microbiology*; D051379:Mice; D010020:Osteonecrosis / Q000139:chemically induced / Q000382:microbiology*; D000077268:Pamidronate; D013530:Surgical Wound Infection / Q000188:drug therapy / Q000382:microbiology*; D014081:Tooth Extraction / Q000009:adverse effects
chemical_list: D000900:Anti-Bacterial Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D051523:Fibroblast Growth Factor 7; D000077268:Pamidronate