Inhibition of cyclooxygenase-2 impacts chondrocyte hypertrophic differentiation during endochondral ossification

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Skeletogenesis and bone fracture healing involve endochondral ossification, a process during which cartilaginous primordia are gradually replaced by bone tissue. In line with a role for cyclooxygenase-2 (COX-2) in the endochondral ossification process, non-steroidal anti-inflammatory drugs (NSAIDs) were reported to negatively affect bone fracture healing due to impaired osteogenesis. However, a role for COX-2 activity in the chondrogenic phase of endochondral ossification has not been addressed before. We show that COX-2 activity fulfils an important regulatory function in chondrocyte hypertrophic differentiation. Our data reveal essential cross-talk between COX-2 and bone morphogenic protein-2 (BMP-2) during chondrocyte hypertrophic differentiation. BMP-2 mediated chondrocyte hypertrophy is associated with increased COX-2 expression and pharmacological inhibition of COX-2 activity by NSAIDs (e.g., Celecoxib) decreases hypertrophic differentiation in various chondrogenic models in vitro and in vivo, while leaving early chondrogenic development unaltered. Our findings demonstrate that COX-2 activity is a novel factor partaking in chondrocyte hypertrophy in the context of endochondral ossification and these observations provide a novel etiological perspective on the adverse effects of NSAIDs on bone fracture healing and have important implications for the use of NSAIDs during endochondral skeletal development.

Original languageEnglish
Pages (from-to)420-36; discussion 436-7
JournalEuropean Cells & Materials
Volume22
Publication statusPublished - 19 Dec 2011

Keywords

  • Alkaline Phosphatase
  • Animals
  • Antigens, Differentiation
  • Bone Morphogenetic Protein 2
  • Celecoxib
  • Cell Differentiation
  • Cell Enlargement
  • Cell Line
  • Cell Proliferation
  • Chondrocytes
  • Collagen Type II
  • Collagen Type X
  • Core Binding Factor Alpha 1 Subunit
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Gene Expression
  • Growth Plate
  • Membrane Proteins
  • Mice
  • Osteogenesis
  • Pyrazoles
  • Rabbits
  • Sulfonamides
  • Journal Article
  • Research Support, Non-U.S. Gov't

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