title: Selective cyclooxygenase-2 inhibitor prevents reduction of trabecular bone mass in collagen-induced arthritic mice in association with suppression of RANKL/OPG ratio and IL-6 mRNA expression in synovial tissues but not in bone marrow cells.
abstract: We performed this study to clarify whether celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, prevents trabecular bone mass reduction by suppressing arthritis-related increase of bone resorption, and to discriminate differences in actions on bone among celecoxib, SC-58560 (a selective COX-1 inhibitor), and indomethacin. Eight-week-old DBA/1J male mice were divided into six groups as follows. Control untreated (Normal) and collagen-induced arthritic (CIA) mice were compared with four treatment groups: celecoxib was orally administered to CIA mice at doses of 0 (Vehicle), 16 (COX2L), and 75 (COX2H) mg/kg, in addition to two groups of mice treated with SC-58560 (COX1) or indomethacin (IND). Histomorphometry showed a significant decrease in tibial trabecular bone volume in arthritic mice, which was corrected by COX2H. The increased osteoclast surface and number in the Vehicle group were suppressed by COX2L, COX2H, and IND. The decreased bone formation rate in Vehicle was elevated by COX2H without statistical significance. A high ratio of mRNA expression of receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG) in Vehicle synovial tissue was suppressed by COX2L and COX2H. The increased expression of interleukin (IL)-6 mRNA in Vehicle was suppressed by COX2L, COX2H, and IND, although no difference in this expression was observed in bone marrow cells among all groups. In conclusion, in CIA mice, celecoxib suppresses arthritis-related increase in bone resorption at low and high doses and prevents trabecular bone mass reduction at high doses in association with suppression of osteoclast development in bone marrow through inhibition of RANKL/OPG ratio and IL-6 mRNA expression in inflammatory synovial tissue.
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Taketa
authors.forename: Akinori
authors.initials: A
authors.lastname: Sakai
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Nakai
authors.forename: Kunitaka
authors.initials: K
authors.lastname: Menuki
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Yamane
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000596:Amino Acids / Q000652:urine; D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000503:physiopathology*; D002478:Cells, Cultured; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D015675:Osteocalcin / Q000097:blood; D053244:Osteoprotegerin / Q000235:genetics* / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000378:metabolism*; D013977:Tibia / Q000187:drug effects / Q000503:physiopathology
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D015850:Interleukin-6; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D015675:Osteocalcin; C036020:deoxypyridinoline