Enhanced M1/M2 Macrophage Ratio Promotes Orthodontic Root Resorption

作者：Dongfeng He, Xiaoxing Kou, Qing Luo, Ruili Yang, Dongdong Liu, X. Wang, Yingquan Song, Haipeng Cao, Maomao Zeng, Yehua Gan, Yanheng Zhou · 发表于：Journal of Dental Research · 年份：2014 · DOI：10.1177/0022034514553817 · 被引用次数：149 · 研究领域：Oral microbiology and periodontitis research、Bone Metabolism and Diseases、Immune Response and Inflammation

Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophage...