Study on the molecular mechanism of alveolus bone resorption induced periodontal diseases

“利用双杂交系统鉴定TRAF6相互作用分子”、“牙周病动物模型的建立”、“利用动物模型建立牙周病的治疗方法”等研究项目目前正在我室进行。其他研究结果如下：1.利用MyD88基因缺陷小鼠和TRIF基因缺陷小鼠，内毒素和IL-1诱导的成骨细胞RANKL的表达只需要MyD88信号，而不需要TRIF信号。2.Nod2参与了MDP的胞内受体S诱导的成骨细胞RANKL的表达。3.PGE_2直接作用于小鼠破骨祖细胞，促进其向破骨细胞的分化。另一方面，当EP4被转导入破骨细胞后，如降钙素一样，PGE_2通过cAMP-PKA信号抑制破骨细胞的凹坑形成活性。4.建立体外培养的人破骨细胞形成体系，并检测降钙素对破骨细胞的影响。降钙素诱导的人破骨细胞功能需要PKA和PKC两种信号。此外，前列腺素E_2强烈抑制人破骨细胞前体细胞向破骨细胞的分化。前列腺素E_2刺激破骨细胞前体细胞产生抑制因子(S)，并抑制其向破骨细胞的分化。5.利用OPG缺陷小鼠和RANKL缺陷小鼠，我们检测了骨形态发生蛋白2(BMP-2)诱导的异位骨中破骨细胞的形成。研究表明，成骨细胞为RANKL的作用提供了关键的微环境。

The research projects "Identification of the TRAF6 interacting molecules by using the two-hybrid system", "Establishments of animal models for periodontal diseases", and "Development of the treatment method for periodontal diseases using the animal models" are currently performed in our laboratory. The results of the other projects were as follows.1.Using MyD88 deficient mice and TRIF deficient mice, the RANKL expression induced by LPS and IL-1 in osteoblasts required only the MyD88 signals but not TRIF signals2.Nod2 is s involved in RANKL expression in osteoblasts induced by muramyl dipeptide (MDP), a component of peptidoglycan, as an intracellular receptor for MDP.3.PGE_2 directly acts on murine osteoclast progenitors and enhances their differentiation into osteoclasts induced by RANKL. On the other hand, when EP4 was transduced into osteoclasts, like calcitonin, PGE_2 inhibited pit-forming activity of osteoclasts through cAMP-PKA signals.4.In vitro culture systems for human osteoclast formation was established, and effects of calcitonin on human osteoclasts were examined. Both PKA- and PKC-mediated signals were required for the calcitonin-induced human osteoclast function. In addition, PGE_2 strongly inhibits the differentiation of human osteoclast progenitors into osteoclasts. PGE_2 stimulates the production of an inhibitory factor(s) by human osteoclast progenitors, and inhibits their differentiation into osteoclasts.5.Using OPG deficient mice and RANKL deficient mice, we examined osteoclast formation in ectopic bone induced by bone morphogenetic protein 2 (BMP-2). It was shown that osteoblasts provide the critical microenvironment for the action of RANKL.