Naringenin inhibits human osteoclastogenesis and osteoclastic bone resorption.
OBJECTIVE
Naringenin, a naturally occurring flavonoid, possesses a wide range of pharmacological properties. The purpose of this study was to investigate the effect of naringenin on human osteoclastogenesis and osteoclastic bone resorption.


METHODS
Naringenin was tested in a human osteoclastogenesis model using primary osteoclast precursor cells activated by receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for 6 days. Osteoclastogenesis was assessed by determining the number of tartrate-resistant acid phosphatase (TRAP)-stained multinuclear cells, while the secretion of factors involved in osteoclastogenesis was assessed using enzyme-linked immunosorbent assays. The effect of naringenin on bone resorption was investigated using an OsteoAssay human bone plate coupled with an immunoassay to evaluate the release of helical peptide 620-633 from the alpha1 chain of type I collagen.


RESULTS
Naringenin was non-toxic at the highest concentration used (50 microg/ml). Naringenin (10, 25 and 50 microg/ml) significantly inhibited osteoclastogenesis (by 29 +/- 5, 57 +/- 8 and 96 +/- 1%, respectively). Naringenin also markedly inhibited the secretion of interleukin (IL)-1alpha (by 59%), IL-23 (by 87%) and monocyte chemoattractant protein-1 (by 58%). Lastly, naringenin (10, 25 and 50 microg/ml) significantly decreased the release of helical peptide 620-633, an indicator of bone resorption activity (by 44 +/- 0.5, 73 +/- 0.5 and 86 +/- 1%, respectively).


CONCLUSIONS
Naringenin can inhibit human osteoclastogenesis and osteoclastic bone resorption. It thus holds promise as a therapeutic or preventive agent for bone-related diseases such as periodontitis.
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Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire, Université Laval, 2420 Rue de la Terrasse, Quebec City, Quebec, Canada.
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Grenier
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D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001862:Bone Resorption / Q000188:drug therapy*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D053582:Interleukin-1alpha / Q000037:antagonists & inhibitors; D053759:Interleukin-23 / Q000037:antagonists & inhibitors; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects*; D053245:RANK Ligand / Q000378:metabolism
D050071:Bone Density Conservation Agents; D018932:Chemokine CCL2; D044950:Flavanones; D053582:Interleukin-1alpha; D053759:Interleukin-23; D053245:RANK Ligand; D016173:Macrophage Colony-Stimulating Factor; C005273:naringenin