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MIF 诱导破骨细胞分化,并促进小鼠牙周病的进展。

MIF induces osteoclast differentiation and contributes to progression of periodontal disease in mice.

机构信息

Department of Microbiology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

出版信息

Microbes Infect. 2012 Feb;14(2):198-206. doi: 10.1016/j.micinf.2011.09.005. Epub 2011 Oct 6.

DOI:10.1016/j.micinf.2011.09.005
PMID:22016007
Abstract

Periodontal disease (PD) is a chronic inflammatory and alveolar bone destructive disease triggered by microorganisms from the oral biofilm. Oral inoculation of mice with the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) induces marked alveolar bone loss and local production of inflammatory mediators, including Macrophage Migration Inhibitory Factor (MIF). The role of MIF for alveolar bone resorption during PD is not known. In the present study, experimental PD was induced in BALB/c wild-type mice (WT) and MIF knockout mice (MIF⁻/⁻) through oral inoculation of Aa. Despite enhanced number of bacteria, MIF⁻/⁻ mice had reduced infiltration of TRAP-positive cells and reduced alveolar bone loss. This was associated with decreased neutrophil accumulation and increased levels of IL-10 in periodontal tissues. TNF-α production was similar in both groups. In vitro, LPS from Aa enhanced osteoclastic activity in a MIF-dependent manner. In conclusion, MIF has role in controlling bacterial growth in the context of PD but contributes more significantly to the progression of bone loss during PD by directly affecting differentiation and activity of osteoclasts.

摘要

牙周病(PD)是一种由口腔生物膜中的微生物引发的慢性炎症性和牙槽骨破坏性疾病。将牙周病原体伴放线放线杆菌(Aa)口腔接种于小鼠可诱导明显的牙槽骨丢失和局部炎症介质的产生,包括巨噬细胞移动抑制因子(MIF)。MIF 在 PD 期间对牙槽骨吸收的作用尚不清楚。在本研究中,通过 Aa 的口腔接种,在 BALB/c 野生型小鼠(WT)和 MIF 敲除小鼠(MIF⁻/⁻)中诱导实验性 PD。尽管细菌数量增加,但 MIF⁻/⁻小鼠的 TRAP 阳性细胞浸润减少,牙槽骨丢失减少。这与牙周组织中中性粒细胞积聚减少和 IL-10 水平增加有关。两组 TNF-α 的产生相似。在体外,Aa 的 LPS 以 MIF 依赖的方式增强破骨细胞活性。总之,MIF 在 PD 中控制细菌生长方面起作用,但通过直接影响破骨细胞的分化和活性,对 PD 期间骨丢失的进展有更重要的贡献。

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