A specific modulatory effect of PUFAs (polyunsaturated fatty acids) on gene expression of some cytokines involved in bone remodelling has been reported previously. In particular, although a direct action of AA (arachidonic acid) on bone cytokine gene expression has been shown in human osteoblastic cells, OA (oleic acid) and EPA (eicosapentaenoic acid) were ineffective. Since the NO (nitric oxide) system has also been shown to have an important modulatory activity on osteoblasts, osteoclasts and bone metabolism, in the present study we have investigated the effects of PUFAs on iNOS (inducible NO synthase) gene expression in a human osteoblast-like cell line. AA induced a significant increase in iNOS mRNA expression, whereas EPA and OA had no stimulatory effects but instead caused a significant inhibition of AA-induced iNOS gene expression. Blocking of the COX (cyclo-oxygenase) pathway did not inhibit AA-induced iNOS expression. AA action was inhibited instead by the addition of calphostin C and genistein, inhibitors of PKC (protein kinase C) and tyrosine kinases respectively. Experiments performed with specific anti-cytokine antibodies showed a significant decrease in iNOS expression in AA-treated osteoblastic cells, suggesting that both cytokine-dependent and -independent mechanisms account for the effects of AA on iNOS gene expression. In conclusion, our investigation clearly shows specific effects of PUFAs on iNOS expression in human osteoblast-like cells with a cytokine-dependent and -independent mechanism. These results might have clinical relevance and are of interest for understanding the reported beneficial effects of dietary PUFA manipulation on the prevention and/or treatment of primary and secondary bone disease.
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August 2005
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Research Article|
July 25 2005
Specific effect of arachidonic acid on inducible nitric oxide synthase mRNA expression in human osteoblastic cells
Giovanna Priante;
Giovanna Priante
*Department of Medical and Surgical Sciences, University of Padua, via Giustiniani 2, 35128 Padova, Italy
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Estella Musacchio;
Estella Musacchio
*Department of Medical and Surgical Sciences, University of Padua, via Giustiniani 2, 35128 Padova, Italy
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Elisa Pagnin;
Elisa Pagnin
†Clinical and Experimental Medicine, University of Padua, via Giustiniani 2, 35128 Padova, Italy
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Lorenzo A. Calò;
Lorenzo A. Calò
†Clinical and Experimental Medicine, University of Padua, via Giustiniani 2, 35128 Padova, Italy
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Bruno Baggio
*Department of Medical and Surgical Sciences, University of Padua, via Giustiniani 2, 35128 Padova, Italy
Correspondence: Professor Bruno Baggio (email [email protected]).
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Publisher: Portland Press Ltd
Received:
December 20 2004
Revision Received:
February 14 2005
Accepted:
April 01 2005
Accepted Manuscript online:
April 01 2005
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2005
Clin Sci (Lond) (2005) 109 (2): 177–182.
Article history
Received:
December 20 2004
Revision Received:
February 14 2005
Accepted:
April 01 2005
Accepted Manuscript online:
April 01 2005
Citation
Giovanna Priante, Estella Musacchio, Elisa Pagnin, Lorenzo A. Calò, Bruno Baggio; Specific effect of arachidonic acid on inducible nitric oxide synthase mRNA expression in human osteoblastic cells. Clin Sci (Lond) 1 August 2005; 109 (2): 177–182. doi: https://doi.org/10.1042/CS20040369
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