Cyclooxygenase-2 selective inhibition suppresses restoration of tibial trabecular bone formation in association with restriction of osteoblast maturation in skeletal reloading after hindlimb elevation of mice.
To clarify the role of cyclooxygenase-2 (COX-2) in acute recovery of trabecular bone in reloaded hindlimbs of tail-suspended mice, we administered a COX-2 selective inhibitor in the mice during the reloading period after unloading. Experiments were conducted on 140 male C57BL/6J mice (8 weeks old). They were divided into ground control (GC) and unloading by tail suspension (UL) groups. On day 7, Group GC was divided into Groups GC+Vehicle (Veh) and GC+Celecoxib (Cel), while Group UL mice were fed on the ground [reloading (RL)] after 7-day unloading and were then divided into Groups RL+Veh and RL+Cel. Bone histomorphometry, osteogenic cell development, and mRNA expression of osteogenic molecules were assessed. At 5 days after reloading, the increase of bone formation rate and the ratio of osteocalcin mRNA expression per CFU-f colony in Group RL+Cel were significantly decreased compared with those in Group RL+Veh, while alkaline phosphatase-positive (ALP+) CFU-f formation and the ratios of cbfa-1, osterix, and type 1 collagen mRNA expression per CFU-f colony increased to the same levels in both RL groups. At 14 days after reloading, decreased bone volume by unloading in RL+Veh recovered to the same level as that of GC+Veh, but that in RL+Cel did not recover completely. The increase of c-fos mRNA expression in bone marrow cells at 1, 24, and 48 h after reloading, osteocalcin mRNA at 6 h, and osterix mRNA at 24 h were suppressed by COX-2 inhibitor. These data indicate that the COX-2 selective inhibitor celecoxib suppresses the restoration of tibial trabecular bone formation and the acute recovery of trabecular bone. These actions are closely related to restriction of c-fos and osteocalcin mRNA expressions and osteoblast differentiation in bone marrow cells.
Department of Orthopedic Surgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. k-nakai@med.uoeh-u.ac.jp
Kenichiro
K
Nakai
Shinya
S
Tanaka
Akinori
A
Sakai
Masato
M
Nagashima
Masahiro
M
Tanaka
Hajime
H
Otomo
Toshitaka
T
Nakamura
D000818:Animals; D001835:Body Weight; D001846:Bone Development / Q000187:drug effects; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013314:Stress, Mechanical; D013449:Sulfonamides / Q000494:pharmacology*; D013977:Tibia / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D000068579:Celecoxib