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

背景）众所周知，全身炎症后继发性骨质疏松症，如类风湿性关节炎，是由于破骨细胞加速骨吸收所致。最近报道，环氧合酶2（Cox 2）选择性拮抗剂激活p21，导致细胞处于细胞周期的静止期，并引起细胞周期停滞。本研究的目的是明确在全身炎症中，Cox 2抑制剂激活p21抑制破骨细胞对骨吸收的可能性。目的）给全身炎症的小鼠注射Cox 2选择性抑制剂，观察细胞因子和骨代谢的变化。用1剂Cox 1选择性拮抗剂、2剂Cox 2选择性拮抗剂、1剂吲哚美辛或仅载体治疗。校正尿液和血清以检测骨吸收和骨形成标志物。在第21个<st>实验日， 关于我们 结果）Cox 2选择性抑制剂可抑制AA小鼠骨吸收的增加，并抑制IL-1β和IL-6表达的增加。AA小鼠骨形成减少，各组间无差异。AA小鼠关节组织中RANKL mRNA/OPG mRNA表达比例和TRACP mRNA表达量增加，IFN-γ mRNA表达量减少。骨钙素-p21转基因小鼠和野生型小鼠关节炎评分和骨密度值无显著性差异。讨论）关节组织中IL-1β和IL-6升高，IFN-γ降低，导致骨小梁和受累部位RANKL/OPG表达比例增加，骨吸收增加。提示Cox 2选择性抑制剂可能通过阻滞细胞周期而抑制AA小鼠骨吸收。少

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