Department of Oral Biology, BK21 Project, Oral Science Research Center, Research Center for Orofacial Hard Tissue Regeneration, Yonsei University College of Dentistry, Seoul, Korea.
J Periodontal Res. 2010 Dec;45(6):772-9. doi: 10.1111/j.1600-0765.2010.01298.x.
Periodontitis is a chronic inflammatory disease of the periodontium that causes significant alveolar bone loss. Osteoclasts are bone-resorbing multinucleated cells. Osteoblasts regulate osteoclast differentiation by expression of RANKL and osteoprotegerin (OPG). Td92 is a surface-exposed outer membrane protein of Treponema denticola, a periodontopathogen. Although it has been demonstrated that Td92 acts as a stimulator of various proinflammatory mediators, the role of Td92 in alveolar bone resorption remains unclear. Therefore, in this study, we investigated the role of Td92 in bone resorption.
Mouse bone marrow cells were co-cultured with calvariae-derived osteoblasts in the presence or absence of Td92. Osteoclast formation was assessed by TRAP staining. Expressions of RANKL, osteoprotegerin (OPG) and prostaglandin E(2) (PGE(2) ) in osteoblasts were estimated by ELISA.
Td92 induced osteoclast formation in the co-cultures. In the osteoblasts, RANKL and PGE(2) expressions were up-regulated, whereas OPG expression was down-regulated by Td92. The addition of OPG inhibited Td92-induced osteoclast formation. The prostaglandin synthesis inhibitors NS398 and indomethacin were also shown to inhibit Td92-induced osteoclast formation. The effects of Td92 on the expressions of RANKL, OPG and PGE(2) in osteoblasts were blocked by NS398 or indomethacin.
These results suggest that Td92 promotes osteoclast formation through the regulation of RANKL and OPG production via a PGE(2) -dependent mechanism.
牙周炎是一种慢性牙周组织炎症性疾病，可导致显著的牙槽骨丧失。破骨细胞是一种具有骨吸收功能的多核细胞。成骨细胞通过表达 RANKL 和骨保护素（OPG）来调节破骨细胞的分化。Td92 是牙周致病菌齿垢密螺旋体的一种表面暴露的外膜蛋白。尽管已经证明 Td92 作为各种促炎介质的刺激物发挥作用，但 Td92 在牙槽骨吸收中的作用尚不清楚。因此，在本研究中，我们研究了 Td92 在骨吸收中的作用。
在存在或不存在 Td92 的情况下，将小鼠骨髓细胞与颅骨来源的成骨细胞共培养。通过 TRAP 染色评估破骨细胞形成。通过 ELISA 评估成骨细胞中 RANKL、骨保护素（OPG）和前列腺素 E2（PGE2）的表达。
Td92 诱导共培养物中的破骨细胞形成。在成骨细胞中，Td92 上调了 RANKL 和 PGE2 的表达，而下调了 OPG 的表达。OPG 的添加抑制了 Td92 诱导的破骨细胞形成。前列腺素合成抑制剂 NS398 和吲哚美辛也显示出抑制 Td92 诱导的破骨细胞形成的作用。NS398 或吲哚美辛阻断了 Td92 对成骨细胞中 RANKL、OPG 和 PGE2 表达的影响。
这些结果表明，Td92 通过 PGE2 依赖性机制调节 RANKL 和 OPG 的产生来促进破骨细胞的形成。
