Inhibition of COX-2 Pathway as a Potential Prophylaxis Against Arthrofibrogenesis in a Rabbit Model of Joint Contracture

Christopher G. Salib, Nicolas Reina, William H. Trousdale, Afton K. Limberg, Megan E. Tibbo, Anthony G. Jay, Joseph X. Robin, Travis W. Turner, Carter R. Jones, Christopher R. Paradise, Eric A. Lewallen, Brad Bolon, Jodi M. Carter, Daniel J. Berry, Mark E. Morrey, Joaquin Sanchez-Sotelo, Andre J. van Wijnen, Matthew P. Abdel

Research output: Contribution to journalArticle

Abstract

Arthrofibrosis is a common complication following total knee arthroplasty caused by pathologic fibroblast activation and excessive collagen deposition around a synovial joint leading to debilitating loss of motion. Treatment options are limited because the pathologic mechanisms remain to be characterized. Dysregulation of the inflammatory cascade may lead to communication between myofibroblasts and immune cells triggering tissue metaplasia, and excessive collagen deposition described clinically as arthrofibrosis. We explored the novel use of celecoxib (selective cyclooxygenase-2 [COX-2] inhibitor) to disrupt the downstream effects of the post-traumatic inflammatory cascade and inhibit scar tissue formation in a validated rabbit model of arthrofibrosis combined with new parameters for quantifying the stiffness of the posterior capsule. Biomechanical and molecular analyses, of contracted rabbit knee posterior capsule tissue after COX-2 inhibition revealed increased maximal passive extension and down-regulation of collagen messenger RNA compared with controls. Histopathologic examination suggested a trend of decreased quantities of dense fibrous connective tissue with COX-2 inhibition. These data may suggest that inhibiting the inflammatory cascade could potentially reduce pathologic myofibroblast activation, thereby reducing scar tissue formation and increasing the range of motion in arthrofibrotic joints. Implementing a multi-modal pharmacologic approach may simultaneously target numerous cellular components contributing to the complex process of arthrofibrogenesis.

Original languageEnglish (US)
JournalJournal of Orthopaedic Research
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Contracture
Cyclooxygenase 2
Joints
Rabbits
Collagen
Myofibroblasts
Celecoxib
Capsules
Cicatrix
Knee Replacement Arthroplasties
Cyclooxygenase 2 Inhibitors
Metaplasia
Articular Range of Motion
Connective Tissue
Knee
Down-Regulation
Fibroblasts
Communication
Messenger RNA
Inhibition (Psychology)

Keywords

  • arthrofibrosis
  • celecoxib
  • COX-2 inhibition
  • myofibroblast
  • total knee arthroplasty

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Inhibition of COX-2 Pathway as a Potential Prophylaxis Against Arthrofibrogenesis in a Rabbit Model of Joint Contracture. / Salib, Christopher G.; Reina, Nicolas; Trousdale, William H.; Limberg, Afton K.; Tibbo, Megan E.; Jay, Anthony G.; Robin, Joseph X.; Turner, Travis W.; Jones, Carter R.; Paradise, Christopher R.; Lewallen, Eric A.; Bolon, Brad; Carter, Jodi M.; Berry, Daniel J.; Morrey, Mark E.; Sanchez-Sotelo, Joaquin; van Wijnen, Andre J.; Abdel, Matthew P.

In: Journal of Orthopaedic Research, 01.01.2019.

Research output: Contribution to journalArticle

Salib, CG, Reina, N, Trousdale, WH, Limberg, AK, Tibbo, ME, Jay, AG, Robin, JX, Turner, TW, Jones, CR, Paradise, CR, Lewallen, EA, Bolon, B, Carter, JM, Berry, DJ, Morrey, ME, Sanchez-Sotelo, J, van Wijnen, AJ & Abdel, MP 2019, 'Inhibition of COX-2 Pathway as a Potential Prophylaxis Against Arthrofibrogenesis in a Rabbit Model of Joint Contracture', Journal of Orthopaedic Research. https://doi.org/10.1002/jor.24441
Salib, Christopher G. ; Reina, Nicolas ; Trousdale, William H. ; Limberg, Afton K. ; Tibbo, Megan E. ; Jay, Anthony G. ; Robin, Joseph X. ; Turner, Travis W. ; Jones, Carter R. ; Paradise, Christopher R. ; Lewallen, Eric A. ; Bolon, Brad ; Carter, Jodi M. ; Berry, Daniel J. ; Morrey, Mark E. ; Sanchez-Sotelo, Joaquin ; van Wijnen, Andre J. ; Abdel, Matthew P. / Inhibition of COX-2 Pathway as a Potential Prophylaxis Against Arthrofibrogenesis in a Rabbit Model of Joint Contracture. In: Journal of Orthopaedic Research. 2019.
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