{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T11:45:26Z","timestamp":1778586326133,"version":"3.51.4"},"reference-count":47,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T00:00:00Z","timestamp":1571184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cooperative Research Program for Agriculture Science and Technology Development","award":["PJ013524022018"],"award-info":[{"award-number":["PJ013524022018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Osteoporosis is a disease that leads to reduced bone mineral density. The increase in patient and medical costs because of global aging is recognized as a problem. Decreased bone mass is a common symptom of bone diseases such as Paget\u2019s disease, rheumatoid arthritis, and multiple myeloma. Osteoclasts, which directly affect bone mass, show a marked increase in differentiation and activation in the aforementioned diseases. Moreover, these multinucleated cells made from monocytes\/macrophages under the influence of RANKL and M-CSF, are the only cells capable of resorbing bones. In this study, we found that the water extracts of Boseokchal (BSC-W) inhibited osteoclast differentiation in vitro and investigated its inhibitory mechanism. BSC-W was obtained by extracting flour of Boseokchal using hexane and water. To osteoclast differentiation, bone marrow-derived macrophage cells (BMMs) were cultured with the vehicle (0.1% DMSO) or BSC-W in the presence of M-CSF and RANKL for 4 days. Cytotoxicity was measured by CCK-8. Gene expression of cells was confirmed by real-time PCR. Protein expression of cells was observed by western blot assay. Bone resorption activity of osteoclast evaluated by bone pit formation assay using an Osteo Assay Plate. BSC-W inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner without exerting a cytotoxic effect on BMMs. BSC-W decreased the transcriptional and translational expression of c-Fos and NFATc1, which are regulators of osteoclastogenesis and reduced the mRNA expression level of TRAP, DC-STAMP, and cathepsin K, which are osteoclast differentiation marker. Furthermore, BSC-W reduced the resorption activity of osteoclasts. Taken together, our results indicate that BSC-W is a useful candidate for health functional foods or therapeutic agents that can help treat bone diseases such as osteoporosis.<\/jats:p>","DOI":"10.3390\/molecules24203735","type":"journal-article","created":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T04:46:06Z","timestamp":1571287566000},"page":"3735","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Water Extracts of Hull-less Waxy Barley (Hordeum vulgare L.) Cultivar \u2018Boseokchal\u2019 Inhibit RANKL-induced Osteoclastogenesis"],"prefix":"10.3390","volume":"24","author":[{"given":"Kwang-Jin","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Sunchon National University, Suncheon 57922, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongjin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sunchon National University, Suncheon 57922, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7139-6394","authenticated-orcid":false,"given":"So-Ri","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and technology, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunjin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Jin","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sunchon National University, Suncheon 57922, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6064-5295","authenticated-orcid":false,"given":"Mi-Kyung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Sunchon National University, Jeonnam, Suncheon 57922, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9036-3221","authenticated-orcid":false,"given":"Mija","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Crop Foundation, National Institute of Crop Science (NICS), Rural Development Administration (RDA), Wanju 55365, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/nrd916","article-title":"Discoveries, drugs and skeletal disorders","volume":"1","author":"Goltzman","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1126\/science.289.5484.1508","article-title":"Therapeutic Approaches to Bone Diseases","volume":"289","author":"Rodan","year":"2000","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"NIH Consensus Development (2000). Osteoporosis prevention, diagnosis, and therapy. JAMA, 285, 785\u2013795.","DOI":"10.1001\/jama.285.6.785"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.abb.2008.03.037","article-title":"Osteoclast lineage and function","volume":"473","author":"Vaananen","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast differentiation and activation","volume":"423","author":"Boyle","year":"2003","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1080\/15216540500137669","article-title":"RANKing Intracellular Signaling in Osteoclasts","volume":"57","author":"Feng","year":"2005","journal-title":"IUBMB Life"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/nrc3838","article-title":"Translational biology of osteosarcoma","volume":"14","author":"Kansara","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"34120","DOI":"10.1074\/jbc.273.51.34120","article-title":"The Involvement of Multiple Tumor Necrosis Factor Receptor (TNFR)-associated Factors in the Signaling Mechanisms of Receptor Activator of NF-kappa B, a Member of the TNFR Superfamily","volume":"273","author":"Galibert","year":"1998","journal-title":"J. Boil. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"28355","DOI":"10.1074\/jbc.273.43.28355","article-title":"The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor","volume":"273","author":"Wong","year":"1998","journal-title":"J. Boil. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1172\/JCI200422644","article-title":"RANKing c-Jun in osteoclast development","volume":"114","author":"Teitelbaum","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1196\/annals.1402.071","article-title":"The Role of NFAT in Osteoclast Formation","volume":"1116","author":"Takayanagi","year":"2007","journal-title":"Ann. New York Acad. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/nri2062","article-title":"Osteoimmunology: Shared mechanisms and crosstalk between the immune and bone systems","volume":"7","author":"Takayanagi","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/j.0105-2896.2005.00332.x","article-title":"Fos\/AP-1 proteins in bone and the immune system","volume":"208","author":"Wagner","year":"2005","journal-title":"Immunol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"45969","DOI":"10.1074\/jbc.M408795200","article-title":"Essential Role of p38 Mitogen-activated Protein Kinase in Cathepsin K Gene Expression during Osteoclastogenesis through Association of NFATc1 and PU.1","volume":"279","author":"Matsumoto","year":"2004","journal-title":"J. Boil. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1084\/jem.20050645","article-title":"DC-STAMP is essential for cell\u2013cell fusion in osteoclasts and foreign body giant cells","volume":"202","author":"Yagi","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1021\/jf030370h","article-title":"Cyanidin and Malvidin from Oryza sativa cv. Heugjinjubyeo mediate cytotoxicity against human monocytic leukemia cells by arrest of G(2)\/M phase and induction of apoptosis","volume":"52","author":"Hyun","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_17","first-page":"173","article-title":"Antioxidant activity of blackish purple rice","volume":"51","author":"Ryu","year":"2006","journal-title":"Korean J. Crop. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ghosh, M., Kim, I.S., Lee, Y.M., Hong, S.M., Lee, T.H., Lim, J.H., Debnath, T., and Lim, B.O. (2018). The Effects of Aronia melanocarpa \u2018Viking\u2019 Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS\/NFATc1 Signaling. Molecules, 23.","DOI":"10.3390\/molecules23030615"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1002\/jcp.24916","article-title":"Dual Effect of Cyanidin on RANKL-Induced Differentiation and Fusion of Osteoclasts","volume":"231","author":"Dou","year":"2016","journal-title":"J. Cell Physiol."},{"key":"ref_20","first-page":"244","article-title":"A new colored naked barley cultivar\u201d Zasoojeongchal\u201d with waxy endosperm","volume":"39","author":"Choi","year":"2007","journal-title":"Korean J. Breed. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"456","DOI":"10.9787\/KJBS.2014.46.4.456","article-title":"Hull-less waxy barley (Hordeum vulgare L.) cultivar \u2018Boseokchal\u2019 with high anthocyanin content and purple lemma","volume":"46","author":"Lee","year":"2014","journal-title":"Korean J. Breed. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1017\/S0007114517002835","article-title":"Jones PJH, Ames NP. Barley beta-glucan reduces blood cholesterol levels via interrupting bile acid metabolism","volume":"118","author":"Wang","year":"2017","journal-title":"Br. J. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0092-8674(02)00699-2","article-title":"NFAT signaling: Choreographing the social lives of cells","volume":"109","author":"Crabtree","year":"2002","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S1534-5807(02)00369-6","article-title":"Induction and Activation of the Transcription Factor NFATc1 (NFAT2) Integrate RANKL Signaling in Terminal Differentiation of Osteoclasts","volume":"3","author":"Takayanagi","year":"2002","journal-title":"Dev. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1101\/gad.1102703","article-title":"Transcriptional regulation by calcium, calcineurin, and NFAT","volume":"17","author":"Hogan","year":"2003","journal-title":"Genes Dev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1084\/jem.20051150","article-title":"Autoamplification of NFATc1 expression determines its essential role in bone homeostasis","volume":"202","author":"Asagiri","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kim, S.-H., Kim, K.-J., Kang, H.J., Son, Y.-J., Choi, S.-W., and Lee, M.-J. (2018). The Dual Role of Oat Bran Water Extract in Bone Homeostasis Through the Regulation of Osteoclastogenesis and Osteoblast Differentiation. Molecules, 23.","DOI":"10.20944\/preprints201811.0363.v1"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.bone.2015.07.023","article-title":"Decursin inhibits osteoclastogenesis by downregulating NFATc1 and blocking fusion of pre-osteoclasts","volume":"81","author":"Kim","year":"2015","journal-title":"Bone"},{"key":"ref_29","first-page":"365","article-title":"Primer3 on the WWW for general users and for biologist programmers","volume":"132","author":"Rozen","year":"2000","journal-title":"Methods Mol. Boil."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.3390\/md12042054","article-title":"Placotylene A, an inhibitor of the receptor activator of nuclear factor-kappaB ligand-induced osteoclast differentiation, from a Korean sponge Placospongia sp.","volume":"12","author":"Kim","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1007\/s00198-006-0172-4","article-title":"An estimate of the worldwide prevalence and disability associated with osteoporotic fractures","volume":"17","author":"Johnell","year":"2006","journal-title":"Osteoporos. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrrheum.2009.260","article-title":"Osteoporosis: Impact on health and economics","volume":"6","author":"Harvey","year":"2010","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1093\/gerona\/glt093","article-title":"Public Health Impact of Osteoporosis","volume":"68","author":"Cauley","year":"2013","journal-title":"J. Gerontol. A Boil. Sci. Med. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1254\/jphs.11082FP","article-title":"Tea polyphenols inhibit rat osteoclast formation and differentiation","volume":"118","author":"Oka","year":"2012","journal-title":"J. Pharmacol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Londzin, P., Siudak, S., Cegie\u0142a, U., Pytlik, M., Janas, A., Walig\u00f3ra, A., and Folwarczna, J. (2018). Phloridzin, an Apple Polyphenol, Exerted Unfavorable Effects on Bone and Muscle in an Experimental Model of Type 2 Diabetes in Rats. Nutrients, 10.","DOI":"10.3390\/nu10111701"},{"key":"ref_37","first-page":"202","article-title":"Resveratrol prevents osteoporosis by upregulating FoxO1 transcriptional activity","volume":"41","author":"Feng","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104280","DOI":"10.1016\/j.fitote.2019.104280","article-title":"Identification and structure-activity relationship (SAR) of chemical constituents from Daemonorops draco (Willd.) Blume and selected commercial flavonoids on anti-osteoclastogenesis activity","volume":"138","author":"Wang","year":"2019","journal-title":"Fitoterapia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fphar.2018.01251","article-title":"Effect of Total Flavonoids of Rhizoma drynariae on Tibial Dyschondroplasia by Regulating BMP-2 and Runx2 Expression in Chickens","volume":"9","author":"Yao","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.nut.2017.12.003","article-title":"Dietary flavonoid kaempferol inhibits glucocorticoid-induced bone loss by promoting osteoblast survival","volume":"53","author":"Adhikary","year":"2018","journal-title":"Nutrition"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1126\/science.289.5484.1504","article-title":"Bone resorption by osteoclasts","volume":"289","author":"Teitelbaum","year":"2000","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.indcrop.2017.09.049","article-title":"Verification of the antioxidant activity of a subterranean part of Suaeda japonica Makino","volume":"109","author":"Kang","year":"2017","journal-title":"Ind. Crop. Prod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1002\/jsfa.5633","article-title":"High-throughput micro plate assays for screening flavonoid content and DPPH-scavenging activity in sorghum bran and flour","volume":"92","author":"Herald","year":"2012","journal-title":"J. Sci. Food Agric."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1126\/science.7939685","article-title":"c-Fos: A key regulator of osteoclast-macrophage lineage determination and bone remodeling","volume":"266","author":"Grigoriadis","year":"1994","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"11077","DOI":"10.1074\/jbc.M111696200","article-title":"Microphthalmia transcription factor is a target of the p38 MAPK pathway in response to receptor activator of NF-kappa B ligand signaling","volume":"277","author":"Mansky","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/jcb.10503","article-title":"Phosphatidylinositol 3-kinase coordinately activates the MEK\/ERK and AKT\/NFkappaB pathways to maintain osteoclast survival","volume":"89","author":"Gingery","year":"2003","journal-title":"J. Cell Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"720","DOI":"10.3945\/jn.115.223206","article-title":"High-Molecular-Weight beta-Glucan Decreases Serum Cholesterol Differentially Based on the CYP7A1 rs3808607 Polymorphism in Mildly Hypercholesterolemic Adults","volume":"146","author":"Wang","year":"2016","journal-title":"J. Nutr."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/20\/3735\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:26:58Z","timestamp":1760189218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/20\/3735"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,16]]},"references-count":47,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["molecules24203735"],"URL":"https:\/\/doi.org\/10.3390\/molecules24203735","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,16]]}}}