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Increased OPG/RANKL ratio in the conditioned medium of soybean-treated osteoblasts suppresses RANKL-induced osteoclast differentiation

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Soybean is a major dietary source of isoflavones, particularly daidzein and genistein, which stimulate osteoblastic functions that are initiated by binding to estrogen receptor (ER)-α and ER-β found on osteoblasts. However, coupled with a low expression of ER-α and ER-β in osteoclasts, the inhibitory effects of soy isoflavones on osteoclast differentiation is likely mediated through paracrine factors produced by osteoblasts. Therefore, in this study, we investigated whether soybean can indirectly inhibit osteoclast differentiation through the modulation of osteoclastic factors produced by osteoblasts. Treatment with soybean extracts increased the levels of osteoprotegerin (OPG) and decreased those of receptor activator of nuclear factor-κB ligand (RANKL) in the conditioned medium (CM) of MC3T3-E1 osteoblasts. Subsequently, the RANKL-induced RAW264.7 osteoclast formation was markedly inhibited by treatment with CM collected from MC3T3-E1 osteoblasts incubated with soybean extracts (S-CM). Similarly, S-CM significantly attenuated the RANKL-induced increase in the mRNA and protein levels of matrix metalloproteinase-9 (MMP-9), a potential biomarker gene of osteoclast differentiation, through the suppression of nuclear factor of activated T cells c1 (NFATc1) activation. Of note, a soybean concentration of 0.001 mg/ml further increased the OPG/RANKL ratio compared to treatment with a 0.1 mg/ml soybean concentration and was overall, more effective at inhibiting RANKL-induced osteoclast formation and MMP-9 expression. Taken together, our data demonstrate that treatment with soybean extracts stimulates the secretion of OPG and inhibits that of RANKL, thus inhibiting RANKL-induced osteoclast differentiation through the suppression of NFATc1 activation.
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Document Type: Research Article

Affiliations: 1: Department of Medical Nutrition, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi 446-701, Republic of Korea 2: Sericultural and Apicultural Materials Division, National Academy of Agricultural Science, RDA, Suwon, Gyeonggi 441-100, Republic of Korea 3: Department of Endocrinology, School of Medicine, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA 4: Radiation Research Division, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 580-185, Republic of Korea 5: Department of Dermatology, School of Medicine, University of California, San Francisco (UCSF), San Francisco, CA 94158, USA

Publication date: January 1, 2014

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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