{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T14:13:55Z","timestamp":1770819235955,"version":"3.50.1"},"reference-count":24,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T00:00:00Z","timestamp":1489449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Bone remodeling, a physiological process characterized by bone formation by osteoblasts and bone resorption by osteoclasts, is important for the maintenance of healthy bone in adult humans. Osteoclasts play a critical role in bone erosion and osteoporosis and are bone-specific multinucleated cells generated through differentiation of monocyte\/macrophage lineage precursors. Receptor activator of NF-\u03baB ligand (RANKL) has been reported to induce osteoclast differentiation. In this study, we explored whether Gracilaria verrucosa extracts (GE) could affect RANKL-mediated osteoclast differentiation. GE significantly inhibited RANKL-activated osteoclast differentiation by inhibiting protein expression of c-fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), vital factors in RANKL-mediated osteoclastogenesis. In addition, GE attenuated ovariectomy-induced bone loss in mice. In summary, GE can prevent osteoclastogenesis and hormone-related bone loss via blockage of c-fos-NFATc1 signaling. Our results suggest that GE may have therapeutic potential in the treatment of postmenopausal osteoporosis.<\/jats:p>","DOI":"10.3390\/jcm6030032","type":"journal-article","created":{"date-parts":[[2017,3,14]],"date-time":"2017-03-14T11:53:52Z","timestamp":1489492432000},"page":"32","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["In Vitro and In Vivo Effects of Gracilaria verrucosa Extracts on Osteoclast Differentiation"],"prefix":"10.3390","volume":"6","author":[{"given":"Kwang-Jin","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Sunchon National University, Jeonnam, Suncheon 57922, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sunchon National University, Jeonnam, Suncheon 57922, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun-Ho","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sunchon National University, Jeonnam, Suncheon 57922, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung-Yun","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sunchon National University, Jeonnam, Suncheon 57922, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Tae","family":"Yee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sunchon National University, Jeonnam, Suncheon 57922, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Jin","family":"Son","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sunchon National University, Jeonnam, Suncheon 57922, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2017,3,14]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/nm1593","article-title":"Skeletal remodeling in health and disease","volume":"13","author":"Zaidi","year":"2007","journal-title":"Nat. Med."},{"key":"ref_3","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_4","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_5","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1210\/edrv.20.3.0367","article-title":"Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families","volume":"20","author":"Suda","year":"1999","journal-title":"Endocr. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s00109-011-0749-z","article-title":"RANKL\/RANK-beyond bones","volume":"89","author":"Hanada","year":"2011","journal-title":"J. Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1146\/annurev.immunol.20.100301.064753","article-title":"RANK-L and RANK: T cells, bone loss, and mammalian evolution","volume":"20","author":"Theill","year":"2002","journal-title":"Ann. Rev. Immunol."},{"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-kappaB, a member of the TNFR superfamily","volume":"273","author":"Galibert","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_9","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. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/BF02411252","article-title":"Bone acid phosphatase: Tartrate-resistant acid phosphatase as a marker of osteoclast function","volume":"34","author":"Minkin","year":"1982","journal-title":"Calcif. Tissue Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s00774-006-0697-9","article-title":"Role of DC-STAMP in cellular fusion of osteoclasts and macrophage giant cells","volume":"24","author":"Yagi","year":"2006","journal-title":"J. Bone Miner. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.foodchem.2012.01.106","article-title":"Prevention of Japanese encephalitis virus infections by low-degree-polymerisation sulfated saccharides from Gracilaria sp. and Monostroma nitidum","volume":"133","author":"Chiu","year":"2012","journal-title":"Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1002\/bit.24599","article-title":"Bio-based production of C2\u2013C6 platform chemicals","volume":"109","author":"Jang","year":"2012","journal-title":"Biotechnol. Bioeng."},{"key":"ref_14","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_15","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\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_16","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. Biol."},{"key":"ref_17","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_18","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_19","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. N. Y. Acad. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrm2083","article-title":"Integrating cell-signalling pathways with NF-kappaB and IKK function","volume":"8","author":"Perkins","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1210\/me.2007-0237","article-title":"NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (DC-STAMP)","volume":"22","author":"Kim","year":"2008","journal-title":"Mol. Endocrinol."},{"key":"ref_23","first-page":"193","article-title":"Overview: Animal models of osteopenia and osteoporosis","volume":"1","author":"Jee","year":"2001","journal-title":"J. Musculoskelet. Neuronal Interact."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jep.2012.11.037","article-title":"The anti-osteoporotic effect of Yijung-tang in an ovariectomized rat model mediated by inhibition of osteoclast differentiation","volume":"146","author":"Kim","year":"2013","journal-title":"J. Ethnopharmacol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/6\/3\/32\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:30:26Z","timestamp":1760207426000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/6\/3\/32"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,14]]},"references-count":24,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,3]]}},"alternative-id":["jcm6030032"],"URL":"https:\/\/doi.org\/10.3390\/jcm6030032","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,14]]}}}