2002
DOI: 10.1172/jci0215681
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Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair

Abstract: Preclinical and clinical studies suggest a possible role for cyclooxygenases in bone repair and create concerns about the use of nonsteroidal antiinflammatory drugs in patients with skeletal injury. We utilized wild-type, COX-1(-/-), and COX-2(-/-) mice to demonstrate that COX-2 plays an essential role in both endochondral and intramembranous bone formation during skeletal repair. The healing of stabilized tibia fractures was significantly delayed in COX-2(-/-) mice compared with COX-1(-/-) and wild-type contr… Show more

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Cited by 558 publications
(271 citation statements)
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“…Prostaglandins also support blood supply to the site of new bone formation by causing vasodilatation and by promoting angiogenesis 31 32. In experiments with COX-2 knockout mice, healing of the stabilised tibia fracture was delayed in comparison with wild-type animals and to COX-1 knockouts 33. Similarly, NSAIDs were able to retard a bone morphogenetic protein 7 induced ectopic bone formation in an experimental mouse model indicating an important role of COX-mediated prostaglandin synthesis in new bone formation 34.…”
Section: Discussionmentioning
confidence: 99%
“…Prostaglandins also support blood supply to the site of new bone formation by causing vasodilatation and by promoting angiogenesis 31 32. In experiments with COX-2 knockout mice, healing of the stabilised tibia fracture was delayed in comparison with wild-type animals and to COX-1 knockouts 33. Similarly, NSAIDs were able to retard a bone morphogenetic protein 7 induced ectopic bone formation in an experimental mouse model indicating an important role of COX-mediated prostaglandin synthesis in new bone formation 34.…”
Section: Discussionmentioning
confidence: 99%
“…The femora and unfractured tibiae were excised, and the soft tissues were removed. Primary bone marrow cells were isolated and prepared as described previously (Franzoso et al 1998; Zhang et al 2002). Bone marrow cells were cultured in α-minimal essential medium (α-MEM) with 10% fetal bovine serum (FBS; Hyclone Laboratories, Logan, UT) and 1% penicillin/streptomycin (Gibco) for 3 days.…”
Section: Methodsmentioning
confidence: 99%
“…Samples were then processed, embedded in paraffin, and cut in 3-μm sagittal sections. Three contiguous sections (100 μm apart) for each specimen were stained with Alcian blue and counterstained with hematoxylin, orange G, and eosin (ABH/OG) as described previously (Zhang et al 2002). Additional contiguous sections were stained for TRAP activity using naphthol AS-BI phosphate and counter-stained with hematoxylin (Sigma).…”
Section: Methodsmentioning
confidence: 99%
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“…Previous evidence suggests that cyclo-oxygenase-2 (COX 2) inhibitors might be more effective in inhibiting ectopic bone formation,9 provide good postoperative pain relief, and cause less bleeding than non-selective inhibitors. They might be an attractive alternative to NSAIDs, but this remains to be confirmed in a randomised controlled trial.…”
mentioning
confidence: 99%