Impairment of the chondrogenic phase of endochondral ossification in vivo by inhibition of cyclooxygenase-2

M.P.F. Janssen, M.M.J. Caron, B. Van Rietbergen, D.A.M. Surtel, L.W. van Rhijn, T.J.M. Welting, P.J. Emans

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Many studies have reported on the effects of cyclooxygenase-2 (COX-2) inhibition on osteogenesis. However, far less is known about the effects of COX-2 inhibition on chondrogenic differentiation. Previous studies conducted by our group show that COX-2 inhibition influences in vitro chondrogenic differentiation. Importantly, this might have consequences on endochondral ossification processes occurring in vivo, such as bone fracture healing, growth plate development and ectopic generation of cartilage. The goal of our study was to investigate, in vivo, the effect of COX-2 inhibition by celecoxib on the cartilaginous phase of three different endochondral ossification scenarios. 10 mg/kg/d celecoxib or placebo were orally administered for 25 d to skeletally-immature New Zealand White rabbits (n = 6 per group). Endochondral ossification during fracture healing of a non-critical size defect in the ulna, femoral growth plate and ectopically-induced cartilaginous tissue were examined by radiography, micro-computed tomography (μ-CT), histology and gene expression analysis. Celecoxib treatment resulted in delayed bone fracture healing, alterations in growth plate development and progression of mineralisation. In addition, chondrogenic differentiation of ectopically-induced cartilaginous tissue was severely impaired by celecoxib. In conclusion, we found that celecoxib impaired the chondrogenic phase of endochondral ossification.

Original languageEnglish
Pages (from-to)202-216
Number of pages15
JournalEuropean Cells and Materials
Volume34
DOIs
Publication statusPublished - 17 Oct 2017

Keywords

  • Celecoxib
  • Chondrogenic differentiation
  • Cyclooxygenase 2
  • Endochondral ossification
  • Fracture healing
  • Growth plate development
  • Nonsteroidal anti-inflammatory drugs

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