title: The Effect of Cyclooxygenase Inhibition on Tendon-Bone Healing in an In Vitro Coculture Model.
abstract: 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.
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Marburg, 35043 Marburg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Schwarting
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Marburg, 35043 Marburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Pretzsch
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Marburg, 35043 Marburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Debus
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Marburg, 35043 Marburg, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Ruchholtz
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, University Hospital Marburg, 35043 Marburg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Lechler
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques / Q000379:methods; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D007052:Ibuprofen / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D013710:Tendons / Q000187:drug effects / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D016861:Cyclooxygenase Inhibitors; D007555:Isoxazoles; D008070:Lipopolysaccharides; C409945:parecoxib; C510878:ALPL protein, mouse; D000469:Alkaline Phosphatase; D007052:Ibuprofen