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

Authors: MPF Janssen, MMJ Caron, B van Rietbergen, DAM Surtel, LW van Rhijn, TJM Welting, PJ Emans

Address: Laboratory for Experimental Orthopaedics, Department of Orthopaedic Surgery, CAPHRI Care and Public Health Research Institute, Maastricht University Medical Centre, PO Box 5800, 6202 AZ Maastricht, the Netherlands

E-mail: marjolein.caron at maastrichtuniversity.nl

Key Words: Endochondral ossification, fracture healing, growth plate development, nonsteroidal anti-inflammatory drugs, cyclooxygenase 2, celecoxib, chondrogenic differentiation.

Publication date: October 17th 2017

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/day 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.

Article download: Pages 202-216 (PDF file)
DOI: 10.22203/eCM.v034a13