The Effect of Cyclooxygenase Inhibition on Tendon-Bone Healing in an In Vitro Coculture Model

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 ibuprofe...

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Main Authors: Tim Schwarting, Sebastian Pretzsch, Florian Debus, Steffen Ruchholtz, Philipp Lechler
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2015/926369
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author Tim Schwarting
Sebastian Pretzsch
Florian Debus
Steffen Ruchholtz
Philipp Lechler
author_facet Tim Schwarting
Sebastian Pretzsch
Florian Debus
Steffen Ruchholtz
Philipp Lechler
author_sort Tim Schwarting
collection DOAJ
description 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.
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spelling doaj-art-b1855f624f674267a4ae5a183d0949662025-02-03T01:32:13ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/926369926369The Effect of Cyclooxygenase Inhibition on Tendon-Bone Healing in an In Vitro Coculture ModelTim Schwarting0Sebastian Pretzsch1Florian Debus2Steffen Ruchholtz3Philipp Lechler4Department of Trauma, Hand and Reconstructive Surgery, University Hospital Marburg, 35043 Marburg, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, University Hospital Marburg, 35043 Marburg, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, University Hospital Marburg, 35043 Marburg, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, University Hospital Marburg, 35043 Marburg, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, University Hospital Marburg, 35043 Marburg, GermanyThe 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.http://dx.doi.org/10.1155/2015/926369
spellingShingle Tim Schwarting
Sebastian Pretzsch
Florian Debus
Steffen Ruchholtz
Philipp Lechler
The Effect of Cyclooxygenase Inhibition on Tendon-Bone Healing in an In Vitro Coculture Model
Mediators of Inflammation
title The Effect of Cyclooxygenase Inhibition on Tendon-Bone Healing in an In Vitro Coculture Model
title_full The Effect of Cyclooxygenase Inhibition on Tendon-Bone Healing in an In Vitro Coculture Model
title_fullStr The Effect of Cyclooxygenase Inhibition on Tendon-Bone Healing in an In Vitro Coculture Model
title_full_unstemmed The Effect of Cyclooxygenase Inhibition on Tendon-Bone Healing in an In Vitro Coculture Model
title_short The Effect of Cyclooxygenase Inhibition on Tendon-Bone Healing in an In Vitro Coculture Model
title_sort effect of cyclooxygenase inhibition on tendon bone healing in an in vitro coculture model
url http://dx.doi.org/10.1155/2015/926369
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