Investigation for participation of cell cycle concerned in osteoporosis followed by chronic inflammation.

研究与骨质疏松症和慢性炎症有关的细胞周期的参与。

• 批准号: 15591608
• 负责人: SHIMIZU Kenji
• 金额: $ 2.43万
• 依托单位: University of Occupational and Environmental Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591608/
• 关键词: P21; cell cycle; arthritis; cytokine; osteoporosis; cyclooxygenase 2; osteoblast; osteoclast; P21; 骨塩量; 卵巣摘出

Back grounds) It is known that secondary osteoporosis after whole body inflammation, eg, rheumatoid arthritis, caused by accelerated bone absorption by osteoclast. It was recently reported that Cyclooxygenase2 (Cox2) selective antagonists activate p21, that leads cells in the quiescent stage in the cell cycle, and cause cell cycle arrest. The purpose of this study is to clear the possibility that activation of p21 by Cox2 inhibitor can suppress the bone absorption by osteoclast in the whole body inflammation.Objective) We administrated Cox2 selective inhibitor to the mouse that has systemic inflammation to examine the changes of cytokines and bone metabolisms.Materials and Methods) 8-w-old male mice induced adjuvant arthritis (AA) using were treated with 1 dose of Cox1 selective antagonists, 2 doses of Cox2 selective antagonists, 1 dose of Indomethacin, or vehicle only. Urine and serum were corrected to test bone absorption and formation marker. At the 21^<st> experimental day, bilater … More al tibiae were harvested to examine histomorphometry and primary bone marrow cell culture.Results) Administration of Cox2 selective inhibitor prevented increased bone absorption and prevent increased IL-1β and IL-6 expression in AA mice. Bone formation decreased in AA mice and there were no difference among all groups. The proportion of RANKL mRNA/OPG mRNA expression and the value of TRACP mRNA expression increased and the values of IFN-γ mRNA expression decreased in the joint tissues of AA mice. There were no significant differences in the values of arthritis score and bone mineral density among osteocalcin-p21 transgenic mice and wild type mice caused adjuvant arthritis.Discussion) Increased IL-1β and IL-6, and decreased IFN-γ in the joint tissues resulted in increases of the proportion of RANKL/OPG expression and bone absorption in trabecular bone as well as in affected parts. It is suggested that Cox2 selective inhibitor might prevent bone absorption in AA mice via cell cycle arrest. Less

背景）众所周知，全身炎症（例如类风湿性关节炎）后的继发性骨质疏松症是由破骨细胞加速骨吸收引起的。最近有报道称，环加氧酶2（Cox2）选择性拮抗剂激活p21，导致细胞处于静止期。本研究的目的是明确Cox2抑制剂激活p21可以抑制全身破骨细胞骨吸收的可能性。目的）对全身炎症小鼠给予Cox2选择性抑制剂，观察细胞因子和骨代谢的变化。材料与方法）用8周龄雄性小鼠诱导佐剂性关节炎（AA），给予1剂量的Cox2选择性抑制剂治疗。校正Cox1选择性拮抗剂、2剂Cox2选择性拮抗剂、1剂吲哚美辛或仅媒介物以测试骨吸收和形成标记物。实验第 21 天，收获胫骨以检查组织形态学和原代骨髓细胞培养。结果）使用 Cox2 选择性抑制剂可防止 AA 小鼠骨吸收增加并防止 IL-1β 和 IL-6 表达增加AA小鼠骨形成减少，各组间无差异，RANKL mRNA/OPG mRNA表达比例和TRACP mRNA表达值增加，IFN-γ mRNA值增加。 AA小鼠关节组织中的表达骨钙素-p21转基因小鼠和野生型小鼠引起的佐剂性关节炎的关节炎评分和骨密度值没有显着差异。讨论）IL-1β和IL-6增加。关节组织中的 IFN-γ 导致 RANKL/OPG 表达比例增加，骨小梁及受影响部位的骨吸收减少，提示 Cox2 选择性抑制剂可能会阻止 AA 的骨吸收。小鼠通过细胞周期停滞。