A Role of Oral Bacteria in Bisphosphonate-induced Osteonecrosis of the Jaw

A Role of Oral Bacteria in Bisphosphonate-induced Osteonecrosis of the Jaw
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DOI:
10.1177/0022034511420430
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发表时间:
2011-11-01
影响因子:
7.6
通讯作者:
Kawai, T.
Kawai, T.
中科院分区:
医学1区
文献类型:
--
作者:
Mawardi, H.;Giro, G.;Kawai, T.

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尚未达成共识,将口腔细菌与双膦酸盐诱导的颌骨坏死 (BONJ) 的发病机制联系起来。因此,本研究在小鼠模型中研究了口腔细菌对 BONJ 样病变发展的影响。在帕米膦酸 (Pam) 治疗的小鼠中,拔牙后口腔感染具核梭杆菌引起了 BONJ 样病变并延迟上皮愈合,但未药物治疗的对照小鼠却没有,而广谱抗生素混合物完全抑制了这两种情况。此外,在体外和体内实验中,Pam 和具核梭杆菌的组合会导致牙龈成纤维细胞 (GF) 死亡,并下调其角质形成细胞生长因子 (KGF) 的产生,从而诱导上皮细胞生长和迁移。因此,在预先暴露于双磷酸盐的牙周组织中,拔牙部位的细菌感染导致 GF 中 KGF 表达减少,导致上皮伤口愈合过程延迟,而抗生素可以缓解这一延迟。
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.