A role of cPLA_2 in the process when extraction socket is repaired.

cPLA_2在提取套接字修复过程中的作用。

• 批准号: 17591965
• 负责人: SUMI Tadateru
• 金额: $ 2.18万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591965/
• 关键词: regenerative medicine; histology and cell biology; signaling passway; radiology; odontology

Osteocasts are believed necessary for the repair of extraction socket.A cPLA_2, metabolite PGE2 has been repoted to be negative regulation of osteoclastic function. However, it is not still uncertain whether cPLA_2 per se is involved in the regulation of osteoclastic activity. In this study, we tested the possibility that cPLA_2 activity is necessary for osteoclastogenesis. Further, we investigated the role of cPLA_2 in the cell-fusion mechanism in multinucleated cell formation of osteoclasts and myocytesChanges in subcellular distributions of cPLA_2 and actin after initiation of multinucleated cell formation.Subcellular localizations of cPLA_2 and actin were analyzed by using a confocal laser scanning microscope. The cPLA_2 and actin were distributed throughout the cytoplasm of non-treated RAW264.7 cells. However, there proteins were predominantly distributed at the periphery of the RANKL-treated RAW264.7 cells.Effects of cPLA_2 inhibition in multinucleated cell formation.Next, we assessed the role of cPLA_2 in the multinucleated cell formation and in the regulation of bone resorption ability of RANKL-treated RAW264.7 cells by using the specific cPLA_2, inhibitors or the cPLA_2 siRNA. We found that the cPLA_2 inhibitors (AACOCF3 and MAFP) or cPLA_2 siRNA significantly inhibited multinucleated cell formation and in vitro bone resorption ability of RAW264.7 cells.cPLA_2 involvement in multinucleated myocyte formation of C2C12 cells.We found that multinucleated myocyte formation in C2C12 was also inhibited by the cPLA_2 inhibitors or RNA interference.Together, these results suggest that cPLA_2 may be deeply involved in osteoclastogenesis and myogenesis. A part of the above results was reported at the 47th Congress on Japanese Society for Oral and Maxillofacial Radiology (May, 2006, Tokyo).

骨铸被认为是拔牙槽修复所必需的。cPLA_2（代谢物 PGE2）已被报道为破骨细胞功能的负调节。然而，cPLA_2本身是否参与破骨细胞活性的调节尚不确定。在这项研究中，我们测试了 cPLA_2 活性对于破骨细胞生成所必需的可能性。此外，我们研究了cPLA_2在破骨细胞和肌细胞多核细胞形成的细胞融合机制中的作用，以及多核细胞形成开始后cPLA_2和肌动蛋白的亚细胞分布变化。使用共聚焦激光扫描显微镜分析了cPLA_2和肌动蛋白的亚细胞定位。 cPLA_2和肌动蛋白分布在未处理的RAW264.7细胞的整个细胞质中。然而，这些蛋白质主要分布在RANKL处理的RAW264.7细胞的外周。cPLA_2抑制对多核细胞形成的影响。接下来，我们利用特定的cPLA_2评估了cPLA_2在RANKL处理的RAW264.7细胞的多核细胞形成和骨吸收能力调节中的作用， 抑制剂或 cPLA_2 siRNA。我们发现cPLA_2抑制剂（AACOCF3和MAFP）或cPLA_2 siRNA显着抑制RAW264.7细胞的多核细胞形成和体外骨吸收能力。cPLA_2参与C2C12细胞的多核肌细胞形成。我们发现C2C12中的多核肌细胞形成也受到抑制 通过 cPLA_2 抑制剂或 RNA 干扰。 总之，这些结果表明 cPLA_2 可能深入参与破骨细胞生成和肌生成。上述结果的一部分已在第47届日本口腔颌面放射线学会大会（2006年5月，东京）上报告。