Roles of osteoclast inhibitory and differentiation factors in periodontal tissue.

许多人因牙周病而失去牙齿。然而，牙周病的预防方法目前还没有建立。破骨细胞分化因子（ODF或RANKL）是破骨细胞生成的关键因子，其诱骗受体骨保护素（OPG）负性调节破骨细胞的生成。这两种基因在成骨细胞系细胞中均有表达，但成骨细胞分化状态与RANKL和OPG表达之间的确切关系尚不清楚，人们认为牙周膜细胞在维持牙周组织内环境稳定和释放细胞因子影响牙槽骨代谢方面起着至关重要的作用。我们发现牙周膜成纤维细胞产生OPG。此外，RANKL诱导破骨细胞前体细胞系RAW264.7细胞中的破骨细胞发育。RT-PCR检测破骨细胞分化标志物的表达。RANKL以剂量依赖性方式增加TRAP、组织蛋白酶K、降钙素受体和NFATc 1 mRNA。在共刺激分子中，RANKL增加了这些细胞中的OSCAR mRNA，尽管PIR-A、PIR-B、TREM 2、TREM 3和DAP 12没有变化。此外，我们还发现牙龈成纤维细胞中有云母等应激诱导分子的表达。这些证据可能表明牙周细菌感染引起牙龈组织中云母的诱导，而诱导的云母可能是牙周组织中破骨细胞生成过程开始的标志。

Many people were lost their tooth by periodontal disease. However preventive method for periodontal disease is not currently established. In order to prevent the lost of tooth in their life, we have to develop the preventive method for periodontal disease.Osteoclast differentiation factor; (ODF or RANKL) is essential for osteoclastogenesis, and its decoy receptor osteoprotegerin (OPG) negatively regulates this process. Both genes are expressed in cells of the osteoblast lineage, but the precise relationship between the state of osteoblast differentiation and RANKL and OPG expression is not clearly defined.It is believed that periodontal ligament cells play a vital role in maintaining the homeostasis of periodontal tissues and release cytokines to affect alveolar bone metabolism. We found that periodontal ligament fibroblasts produced the OPG. Furthermore, RANKL induced osteoclast development in preosteoclasts cell lines, RAW264.7 cells. These cells expressed osteoclast differentiation markers analyzed by RT-PCR. RANKL increased TRAP, cathepsin K, calcitonin receptor and NFATc1 mRNAs dose-dependent manner. Among co-stimulatory molecules, RANKL increased OSCAR mRNA in these cells, although PIR-A, PIR-B, TREM2, TREM3 and DAP12 were not changed. In addition, we found the stress-inducible molecules such as MICA were expressed in gingival fibroblasts. These evidences might indicate that the periodontal bacterial infection in gingival tissue causes the induction of MICA, and the induced MICA may be the marker of the beginning of process in osteoclastogenesis in periodontal tissue.