Review Question - QID 430

Cycloxygenase-2 (COX-2,aka prostaglandin-endoperoxide synthase 2) is an enzyme which converts arachidonic acid to prostaglandin endoperoxide H2. COX-2 is not expressed under normal conditions, but elevated levels are found during general states of inflammation. Zhang et al and Simon et al have both studied the role of COX-2 with regard to fracture healing. Zhang et al created a COX-2 knockout mouse (one which does not express the COX-2 gene). This COX-2 knockout mouse has been shown to heal fractures more slowly than COX-1 knockout mice or normal controls, thus identifying the role of COX-2 in general inflammation and bone repair. Zhang et al hypothesize that COX-2 causes mesenchymal progenitor cells to differentiate into osteoblasts, thus promoting new bone formation. Simon et al showed the delayed effects of fracture healing when animals were treated with COX-2 inhibitors. Gerstenfeld et al. studied the reversibility of COX-2 inhibition on the short term bone healing in an animal model. They found that COX-2 inhibitors block fracture healing more than NSAIDS and the magnitude of this effect is related to the duration of treatment. While specific inhibitors of COX-2 exist, traditional NSAIDs non-specifically inhibit both COX-1 and COX-2 enzymes. In addition to its role in inflammation, COX-2 has been shown to be upregulated in many human cancers such as gallbladder carcinoma.