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The effects of cyclooxygenase (COX) inhibition following the reconstruction of the anterior cruciate ligament remain unclear. We examined the effects of selective COX-2 and nonselective COX inhibition on bone-tendon integration in an  in vitro  model. We measured the dose-dependent effects of ibuprofen and parecoxib on the viability of lipopolysaccharide- (LPS-) stimulated and unstimulated mouse MC3T3-E1 and 3T3 cells, the influence on gene expression at the osteoblast, interface, and fibroblast regions measured by quantitative PCR, and cellular outgrowth assessed on histological sections. Ibuprofen led to a dose-dependent suppression of MC3T3 cell viability, while parecoxib reduced the viability of 3T3 cultures. Exposure to ibuprofen significantly suppressed expression of  Alpl  ( P  < 0.01),  Bglap  ( P  < 0.001), and  Runx2  ( P  < 0.01), and although parecoxib reduced expression of  Alpl  ( P  < 0.001),  Fmod  ( P  < 0.001), and  Runx2  ( P  < 0.01), the expression of  Bglap  was increased ( P  < 0.01). Microscopic analysis showed a reduction in cellular outgrowth in LPS-stimulated cultures following exposure to ibuprofen and parecoxib. Nonselective COX inhibition and the specific inhibition of COX-2 led to region-specific reductions in markers of calcification and cell viability. We suggest further  in vitro  and  in vivo  studies examining the biologic and biomechanical effects of selective and nonselective COX inhibition.

The Effect of Cyclooxygenase Inhibition on Tendon-Bone Healing in anIn VitroCoculture Model