The effects of G-CSF and naproxen sodium on the serum TGF-beta1 level and fracture healing in rat tibias

Life Sci. 2006 Dec 3;80(1):67-73. doi: 10.1016/j.lfs.2006.08.023. Epub 2006 Aug 25.


Local and systemic release of transforming growth factor beta 1 (TGF-beta1) is known to increase during the process of fracture healing and this cytokine stimulates bone healing. The majority of the non steroidal anti inflammatory drugs (NSAIDs) inhibit fracture healing. Granulocyte colony stimulating factor (G-CSF) is a hematopoietic growth factor that stimulates bone marrow. In this study, the effects of the NSAID naproxen sodium, G-CSF, and both of them in combination on the TGF-beta1 serum level in rats with tibia fractures were measured and fracture healing was evaluated by histopathologic and radiologic examination. The TGF-beta1 serum levels obtained on day one (24 h after fracture but before administration of naproxen or G-CSF) were found to be similar in all of the five groups (p > 0.05). At the end of the first week, TGF-beta1 levels were significantly lower in naproxen-treated rats than those of the other groups excluding control (p = 0.002). Similar changes in TGF-beta1 levels were found at the end of the second and fourth weeks. TGF-beta1 levels were significantly higher in G-CSF-treated rats at the end of the first, second and fourth weeks (p < 0.05). Fracture healing scores measured with histopathological and radiological methods were higher in G-CSF-treated rats than in naproxen-treated ones. When both naproxen and G-CSF were given, the scores resumed to normal. The results point to the negative effect of naproxen sodium on fracture healing is due to its decreasing effect on the level of TGF-beta1, which may be a new possible mechanism. Moreover, this negative effect can be inhibited by the use of G-CSF.

MeSH terms

  • Animals
  • Fracture Healing / drug effects*
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Male
  • Naproxen / pharmacology*
  • Rats
  • Rats, Wistar
  • Transforming Growth Factor beta1 / blood*


  • Transforming Growth Factor beta1
  • Granulocyte Colony-Stimulating Factor
  • Naproxen