The Flavonoid Naringenin Inhibits Human Osteoclastogenesis and Osteoclastic Bone Resorption

Objective: Naringenin, a naturally occurring flavonoid found in citrus fruits, possesses a wide range of pharmacological properties, including anticancer, antimutagenic, and antiinflammatory activities. The aim of this study was to investigate the effect of naringenin on human in vitro osteoclastogenesis and osteoclastic bone resorption. Methods: Naringenin (0, 10, 25, 50 µg/ml) was tested in a human osteoclastogenesis model using primary osteoclast precursor cells activated by RANKL and MCSF for 6 days. Osteoclastogenesis was assessed by determination of multinuclear cells that stained for tartrate-resistant acid phosphatase (TRAP) while the secretion of factors involved in osteoclastogenesis was determined by enzyme-linked immunosorbent assays. The effect of naringenin on the osteoclastic bone resorption was investigated using an OsteoAssay human bone plate coupled with an immunoassay for determination of helical peptide 620-633 released from the á1 chain of type I collagen. Results: At the highest concentration used (50 µg/ml), naringenin did not show any toxicity towards human osteoclast precursor cells. When added at final concentrations of 10, 25, and 50 µg/ml, naringenin significantly inhibited osteoclastogenesis (29 ± 5%, 57 ± 8%, and 96 ± 1%, respectively). Naringenin also markedly decreased the secretion of IL-1á (59%), IL-23 (87%), and MCP-1 (58%) by osteoclast precursor cells. When naringenin was added to differentiated osteoclasts cultivated on the human bone plate, the release of collagen peptides, which is an indicator of bone resorption activity, was significantly decreased by naringenin at final concentrations of 10, 25, and 50 µg/ml (44 ± 0.5%, 73 ± 0.5%, and 86 ± 1%, respectively). Conclusions: These results suggest that the flavonoid naringenin can reduce both osteoclast differentiation and bone resorption activity. Therefore, it holds promise as a therapeutic agent for treating bone-related diseases such as periodontitis. This study was supported by the Canadian Institutes of Health Research.