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

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591608
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: University of Occupational and Environmental Health
• Principal Investigator: SHIMIZU Kenji UNIVERSITY OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助手 (60299617)
• Co-Investigator(Kenkyū-buntansha): NAKAMURA Toshitaka UNIVERSITY OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (50082235) ; SAKAI Akinori UNIVERSITY OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (90248576) ; NARUSAWA Ken'ichiro UNIVERSITY OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 講師 (20269062)
• Project Period (FY): 2003 – 2005
• Keywords: P21 / cell cycle / arthritis / cytokine / osteoporosis / cyclooxygenase 2 / osteoblast / osteoclast

Research Abstract

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 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.