Cochran David L
Department of Periodontics, The University of Texas Health Science Center at San Antonio, 7702 Floyd Curl Drive, San Antonio, TX 78229, USA.
J Periodontol. 2008 Aug;79(8 Suppl):1569-76. doi: 10.1902/jop.2008.080233.
Inflammation and bone loss are hallmarks of periodontal disease (PD). The question is how the former leads to the latter. Accumulated evidence demonstrates that PD involves bacterially derived factors and antigens that stimulate a local inflammatory reaction and activation of the innate immune system. Proinflammatory molecules and cytokine networks play essential roles in this process. Interleukin-1 and tumor necrosis factor-alpha seem to be primary molecules that, in turn, influence cells in the lesion. Antigen-stimulated lymphocytes (B and T cells) also seem to be important. Eventually, a cascade of events leads to osteoclastogenesis and subsequent bone loss via the receptor activator of nuclear factor-kappa B (RANK)-RANK ligand (RANKL)-osteoprotegerin (OPG) axis. This axis and its regulation are not unique to PD but rather are critical for pathologic lesions involving chronic inflammation. Multiple lines of evidence in models of PD clearly indicate that increases in RANKL mRNA expression and protein production increase the RANKL/OPG ratio and stimulate the differentiation of macrophage precursor cells into osteoclasts. They also stimulate the maturation and survival of the osteoclast, leading to bone loss. OPG mRNA expression and protein production do not generally seem to be increased in the periodontitis lesion. Studies of RANKL and OPG transgenic and knockout animals provide further support for the involvement of these molecules in the tissue loss observed in PD. Ironically, periodontal practitioners have focused on the bacterial etiology of PD and believed that plaque removal was aimed at eliminating specific bacteria or bacterial complexes. However, it seems that the reduction of inflammation and attenuation of the host's immune reaction to the microbial plaque, eventually leading to a decrease in the ratio of RANKL/OPG and a decrease in associated bone loss, are the actual and desired outcomes of periodontal therapy. Future therapeutic options are likely to have regulation of the RANK-RANKL-OPG axis as their goal.
炎症和骨质流失是牙周病（PD）的标志。问题在于前者如何导致后者。越来越多的证据表明，牙周病涉及细菌衍生的因子和抗原，它们会刺激局部炎症反应并激活先天免疫系统。促炎分子和细胞因子网络在这一过程中起着至关重要的作用。白细胞介素 -1 和肿瘤坏死因子 -α 似乎是主要分子，它们进而影响病变中的细胞。抗原刺激的淋巴细胞（B 细胞和 T 细胞）似乎也很重要。最终，一系列事件通过核因子 -κB 受体激活剂（RANK）-RANK 配体（RANKL）-骨保护素（OPG）轴导致破骨细胞生成及随后的骨质流失。该轴及其调节并非牙周病所特有，而是对涉及慢性炎症的病理病变至关重要。牙周病模型中的多条证据清楚地表明，RANKL mRNA 表达和蛋白质产生的增加会提高 RANKL/OPG 比值，并刺激巨噬细胞前体细胞分化为破骨细胞。它们还会刺激破骨细胞的成熟和存活，导致骨质流失。在牙周炎病变中，OPG mRNA 表达和蛋白质产生通常似乎并未增加。对 RANKL 和 OPG 转基因及基因敲除动物的研究为这些分子参与牙周病中观察到的组织损失提供了进一步支持。具有讽刺意味的是，牙周病从业者一直专注于牙周病的细菌病因，并认为去除牙菌斑旨在消除特定细菌或细菌复合物。然而，似乎减轻炎症以及减弱宿主对微生物牙菌斑的免疫反应，最终导致 RANKL/OPG 比值降低和相关骨质流失减少，才是牙周治疗的实际和期望结果。未来的治疗选择可能会以调节 RANK-RANKL-OPG 轴为目标。
