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

背面）众所周知，全身注射后的继发性骨质疏松症，例如，由破骨细胞加速骨损失引起的类风湿关节炎。最近有报道说，环氧合酶2（COX2）选择性拮抗剂激活p21，该拮抗剂在细胞周期中导致细胞在静止阶段引起细胞，并导致细胞周期停滞。这项研究的目的是清除Cox2抑制剂对P21的激活可以抑制整个体内注射中破骨细胞的骨骼遭受的损伤。我们将COX2选择性抑制剂授予了鼠标，以便使用全身性炎症，以检查具有细胞因子和骨骼代谢的变化的全身性炎症，以检查8-WERATIAL SAMICESS.SMATIESS.SMATIES MALITE）。 COX1选择性拮抗剂的剂量，2剂COX2选择性拮抗剂，1剂吲哚美辛或媒介物。校正尿液和血清以测试骨质流失和形成标记。在21^<st>实验日，收集了双侧……更多的胫骨，以检查组织形态计量法和原代骨髓细胞培养。施用COX2选择性抑制剂可防止骨质流失增加，并防止AA小鼠中IL-1β和IL-6表达增加。 AA小鼠的骨形成减少，所有组之间没有差异。 RANKL mRNA/OPG mRNA表达的比例和TRACP mRNA表达的值增加，IFN-γmRNA表达的值在AA小鼠的关节时机中降低。骨钙素-P21转基因小鼠和野生型小鼠的关节炎评分和骨矿物质密度的值没有显着差异，导致了调节性关节炎。障碍提高了IL-1β和IL-6，关节时机中的IFN-γ增加导致rank/op op骨损失的比例增加，导致了三分之一的表达和骨骼损失。建议COX2选择性抑制剂可以通过细胞周期停滞来防止AA小鼠的骨质流失。较少的