The effects of COX-2 inhibitor during osteogenic differentiation of bone marrow-derived human mesenchymal stem cells

Stem Cells Dev. 2010 Oct;19(10):1523-33. doi: 10.1089/scd.2009.0393.


Cyclooxygenase-2 (COX-2) inhibitors suppress bone repair and bone formation by suppressing angiogenesis as well as potentially interfering with osteoblast and osteoclast functions. In spite of these reports, there is a controversy over the exact effects of COX-2 inhibitors on bone formation processes itself. This work was designed to investigate the effect of COX-2 inhibitor on osteogenesis of human bone marrow-derived mesenchymal stem cells (MSC). MSCs in osteogenesis were treated with COX-2 inhibitor (celecoxib and naproxen) in the absence or presence of interleukin-1β (IL-1β), which was used to induce inflammation. Following differentiation, alkaline phosphatase (ALP) and calcium contents of IL-1β-treated MSC were significantly reduced by high doses of COX-2 inhibitors compared with the low-dose group. However, in non-inflammatory-conditioned MSCs, ALP and calcium contents were not reduced by COX-2 inhibitors. The mRNA expression of Runx2/Cbf alpha 1, Dlx5, and osteocalcin was also decreased by COX-2 inhibitors in inflammatory-conditioned MSCs and showed a significant decrease for the high dose while they remained constant in the non-inflammatory-conditioned MSCs. These data indicate that the osteogenic potential of MSC is inhibited/delayed by the treatment of high-dose NSAIDs under inflammatory conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biomarkers / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / physiology*
  • Celecoxib
  • Cell Differentiation / drug effects*
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Interleukin-1beta / pharmacology
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / physiology*
  • Middle Aged
  • Naproxen / pharmacology
  • Osteogenesis / drug effects*
  • Pyrazoles / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sulfonamides / pharmacology
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Cyclooxygenase 2 Inhibitors
  • Interleukin-1beta
  • Pyrazoles
  • RNA, Messenger
  • Sulfonamides
  • Naproxen
  • Cyclooxygenase 2
  • Celecoxib