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

• Published in: Bone (New York, N.Y.) Vol. 39; no. 1; pp. 83 - 92
• Main Authors: Nakai, Kenichiro, Tanaka, Shinya, Sakai, Akinori, Nagashima, Masato, Tanaka, Masahiro, Otomo, Hajime, Nakamura, Toshitaka
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-07-2006; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Body Weight; Bone Development - drug effects; c- fos; Celecoxib; Cyclooxygenase 2 Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Hindlimb Suspension; Histomorphometry; Male; Mechanical stress; Mice; Mice, Inbred C57BL; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteocalcin; Prostaglandin; Pyrazoles - pharmacology; Random Allocation; RNA, Messenger - metabolism; Stress, Mechanical; Sulfonamides - pharmacology; Tibia - cytology; Tibia - drug effects; Tibia - metabolism; Time Factors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Osteocalcin; Prostaglandin; Histomorphometry; Mechanical stress; c- fos; Prostaglandin-endoperoxide synthase; Hindlimb; Enzyme; Rodentia; c-fos; Vertebrata; Mammalia; Mouse; Tibia; Animal; C-Onc gene; Morphology; Osteoblast; Bone trabeculae; Skeleton; Oxidoreductases
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2005.12.014

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.