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

• Published in: Journal of bone and mineral metabolism Vol. 26; no. 2; pp. 143 - 151
• Main Authors: Taketa, Tomonori, Sakai, Akinori, Tanaka, Shinya, Nakai, Kenichiro, Menuki, Kunitaka, Yamane, Hirotoshi, Tanaka, Kazuhiro, Nakamura, Toshitaka
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.03.2008; Springer; Springer Nature B.V
• Subjects: Amino Acids - urine; Animals; Arthritis, Experimental - physiopathology; Biological and medical sciences; Biomarkers - metabolism; Body Weight - drug effects; Bone and Bones - drug effects; Bone and Bones - physiopathology; Bone marrow; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Bones, joints and connective tissue. Antiinflammatory agents; Cells, Cultured; Cyclooxygenase 2 Inhibitors - pharmacology; Diseases of the osteoarticular system; Gene Expression Regulation - drug effects; Interleukin-6 - genetics; Interleukin-6 - metabolism; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Mice; Miscellaneous. Osteoarticular involvement in other diseases; Organ Size - drug effects; Original Article; Orthopedics; Osteocalcin - blood; Osteoprotegerin - genetics; Osteoprotegerin - metabolism; Pharmacology. Drug treatments; RANK Ligand - genetics; RANK Ligand - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Synovial Membrane - metabolism; Tibia - drug effects; Tibia - physiopathology; cyclooxygenase; RANKL; arthritis; osteoclast; bone marrow; Prostaglandin-endoperoxide synthase; Receptor activator Nfkb ligand; Enzyme; Diseases of the osteoarticular system; Rodentia; Arthritis; Cyclooxygenase 2 inhibitor; Osteoclast; Non steroidal antiinflammatory agent; Interleukin 6; Prevention; Vertebrata; Mammalia; Bone mass; Messenger RNA; Mouse; Synovial membrane; Animal; Collagen; Bone marrow; Bone trabeculae; Oxidoreductases
• ISSN: 0914-8779; 1435-5604
• DOI: 10.1007/s00774-007-0808-2

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-κB 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.