{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:41:29Z","timestamp":1788968489718,"version":"build-2803163510"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T00:00:00Z","timestamp":1623628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2018GXNSFAA050092"],"award-info":[{"award-number":["2018GXNSFAA050092"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology. Postmenopausal osteoporosis (PMOP), which increases the risk of fracture, is the most common bone disease in women. PMOP not only increases the risk of death but also imposes a financial burden on countless families. At present, most of the drugs used to treat osteoporosis have significant side effects, so it is important to find effective anti-osteoporosis medications without major side effects. Sesamolin (Ses) is a kind of natural lignan extracted from sesame oil. Many researches have shown that Ses has anti-inflammatory, antioxidative, and anticancer effects, however it is still unknown whether it has any effect on osteoporosis. In this research, we explored the therapeutic effect of Ses in the process of osteoclast formation and bone resorption and found that Ses effectively inhibited osteoclast formation <jats:italic>in vitro<\/jats:italic> through TRAcP staining and hydroxyapatite resorption assays. Through Western blot analysis of the NF-\u03baB pathway, MAPK pathway, c-Fos and NFATc1, it was found that Ses not only effectively inhibited the activation of NF-\u03baB and MAPK signaling pathways induced by RANKL but also significantly reduced the protein expression of c-Fos and NFATc1. Several genes specifically expressed in osteoclasts were determined by qPCR, and Ses was also found to play a significant inhibitory role on the expression of these genes. Besides, an osteoporosis model induced in ovariectomized (OVX) mice was employed to verify that Ses could effectively reduce bone loss caused by estrogen deficiency <jats:italic>in vivo<\/jats:italic>. In conclusion, Ses showed promise as a new treatment for postmenopausal osteoporosis.<\/jats:p>","DOI":"10.3389\/fphar.2021.664697","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T12:16:02Z","timestamp":1623672962000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-\u03baB and MAPK Signaling Pathways"],"prefix":"10.3389","volume":"12","author":[{"given":"Xue","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiamin","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuangang","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfei","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuoxing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuedong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runfeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiake","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/0002-9343(93)90218-e","article-title":"Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis","volume":"94","author":"Author Anonymous","year":"1993","journal-title":"Am. J. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2377","DOI":"10.1007\/s00198-013-2313-x","article-title":"NF-\u03baB signaling and bone resorption","volume":"24","author":"Abu-Amer","year":"2013","journal-title":"Osteoporos. Int."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1084\/jem.190.12.1741","article-title":"Commitment and differentiation of osteoclast precursor cells by the sequential expression of C-Fms and receptor activator of nuclear factor \u03bab (RANK) receptors","volume":"190","author":"Arai","year":"1999","journal-title":"J. Exp. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"169","DOI":"10.2174\/1389201020666191011151123","article-title":"Inhibitory effect of sesamolin on melanogenesis in B16F10 cells determined by in vitro and molecular docking analyses","volume":"21","author":"Baek","year":"2020","journal-title":"Cpb"},{"key":"B5","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3803\/EnM.2015.30.1.35","article-title":"NF-\u03baB-Mediated regulation of osteoclastogenesis","volume":"30","author":"Boyce","year":"2015","journal-title":"Endocrinol. Metab."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1007\/s00198-009-0835-z","article-title":"Estimated prevalence and patterns of presumed osteoporosis among older Americans based on Medicare data","volume":"20","author":"Cheng","year":"2009","journal-title":"Osteoporos. Int."},{"key":"B7","doi-asserted-by":"publisher","first-page":"45964","DOI":"10.1038\/srep45964","article-title":"p38\u03b1 MAPK regulates proliferation and differentiation of osteoclast progenitors and bone remodeling in an aging-dependent manner","volume":"7","author":"Cong","year":"2017","journal-title":"Sci. Rep."},{"key":"B8","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.gene.2005.12.012","article-title":"NFATc1 regulation of the human \u03b23 integrin promoter in osteoclast differentiation","volume":"372","author":"Crotti","year":"2006","journal-title":"Gene"},{"key":"B9","doi-asserted-by":"publisher","first-page":"4317","DOI":"10.1242\/jcs.00082","article-title":"JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and -independent mechanisms","volume":"115","author":"David","year":"2002","journal-title":"J. Cel Sci"},{"key":"B10","doi-asserted-by":"publisher","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":"B11","doi-asserted-by":"publisher","first-page":"107682","DOI":"10.1016\/j.pharmthera.2020.107682","article-title":"RANKL as a key figure in bridging between the bone and immune system: its physiological functions and potential as a pharmacological target","volume":"218","author":"Honma","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1196\/annals.1338.050","article-title":"Oxidative toxicity in BV-2 microglia cells: sesamolin neuroprotection of H2O2Injury involving activation of p38 mitogen-activated protein kinase","volume":"1042","author":"Hou","year":"2005","journal-title":"Ann. N. Y Acad. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1038\/nm1197-1285","article-title":"Osteopetrosis in mice lacking NF-\u03baB1 and NF-\u03baB2","volume":"3","author":"Iotsova","year":"1997","journal-title":"Nat. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1097\/gme.0b013e31802d976f","article-title":"Association between osteoprotegerin (OPG), receptor activator of nuclear factor-\u03baB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL levels, and bone mineral density in Korean postmenopausal women","volume":"14","author":"Kim","year":"2007","journal-title":"Menopause"},{"key":"B15","doi-asserted-by":"publisher","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":"B16","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.intimp.2018.08.027","article-title":"Sesamolin affects both natural killer cells and cancer cells in order to create an optimal environment for cancer cell sensitization","volume":"64","author":"Lee","year":"2018","journal-title":"Int. Immunopharmacology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.cytogfr.2020.02.003","article-title":"The relationship between bone marrow adipose tissue and bone metabolism in postmenopausal osteoporosis","volume":"52","author":"Li","year":"2020","journal-title":"Cytokine Growth Factor. Rev."},{"key":"B18","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/nrendo.2013.179","article-title":"The role of estrogen and androgen receptors in bone health and disease","volume":"9","author":"Manolagas","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"31155","DOI":"10.1074\/jbc.M001229200","article-title":"Involvement of p38 mitogen-activated protein kinase signaling pathway in osteoclastogenesis mediated by receptor activator of NF-kappa B ligand (RANKL)","volume":"275","author":"Matsumoto","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B20","doi-asserted-by":"publisher","first-page":"26475","DOI":"10.1074\/jbc.M313973200","article-title":"Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos","volume":"279","author":"Matsuo","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1111\/bph.12227","article-title":"Activation of adenosine A(2A)receptor reduces osteoclast formation via PKA- and ERK1\/2-mediated suppression of NF\u03baB nuclear translocation","volume":"169","author":"Mediero","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"723","DOI":"10.3389\/fphar.2019.00723","article-title":"Recovery of sesamin, sesamolin, and minor lignans from sesame oil using solid support-free liquid-liquid extraction and chromatography techniques and evaluation of their enzymatic inhibition properties","volume":"10","author":"Michailidis","year":"2019","journal-title":"Front. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"16568","DOI":"10.1073\/pnas.1308755110","article-title":"HIF1\u03b1 is required for osteoclast activation by estrogen deficiency in postmenopausal osteoporosis","volume":"110","author":"Miyauchi","year":"2013","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1083\/jcb.148.2.333","article-title":"Reciprocal role of ERK and nf-\u03bab pathways in survival and activation of osteoclasts","volume":"148","author":"Miyazaki","year":"2000","journal-title":"J. Cel Biol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1006\/bbrc.1998.9788","article-title":"RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis","volume":"253","author":"Nakagawa","year":"1998","journal-title":"Biochem. Biophysical Res. Commun."},{"key":"B26","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1002\/jbmr.3315","article-title":"Prevalence of osteoporosis and low bone mass among Puerto Rican older adults","volume":"33","author":"Noel","year":"2018","journal-title":"J. Bone Miner Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s00418-018-1636-2","article-title":"Recent advances in osteoclast biology","volume":"149","author":"Ono","year":"2018","journal-title":"Histochem. Cel Biol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"147","DOI":"10.4103\/0973-7847.134249","article-title":"Value addition in sesame: a perspective on bioactive components for enhancing utility and profitability","volume":"8","author":"Pathak","year":"2014","journal-title":"Pharmacogn Rev."},{"key":"B29","doi-asserted-by":"publisher","first-page":"Af01","DOI":"10.7860\/jcdr\/2016\/18648.8433","article-title":"The effects of dietary supplements of calcium, vitamin D and estrogen hormone on serum levels of OPG and RANKL cytokines and their relationship with increased bone density in rats","volume":"10","author":"Piri","year":"2016","journal-title":"Jcdr"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/s0140-6736(10)62349-5","article-title":"Osteoporosis: now and the future","volume":"377","author":"Rachner","year":"2011","journal-title":"The Lancet"},{"key":"B31","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s00223-011-9499-8","article-title":"Adverse reactions and drug-drug interactions in the management of women with postmenopausal osteoporosis","volume":"89","author":"Rizzoli","year":"2011","journal-title":"Calcif Tissue Int."},{"key":"B32","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s11914-007-0005-1","article-title":"Novel osteoclast signaling mechanisms","volume":"5","author":"Shinohara","year":"2007","journal-title":"Curr. Osteoporos. Rep."},{"key":"B33","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1146\/annurev-physiol-021119-034425","article-title":"Osteoclasts provide coupling signals to osteoblast lineage cells through multiple mechanisms","volume":"82","author":"Sims","year":"2020","journal-title":"Annu. Rev. Physiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2435","DOI":"10.1016\/j.febslet.2009.06.047","article-title":"Regulatory mechanism of NFATc1 in RANKL-induced osteoclast activation","volume":"583","author":"Song","year":"2009","journal-title":"FEBS Lett."},{"key":"B35","doi-asserted-by":"publisher","first-page":"65","DOI":"10.11480\/jmds.590301","article-title":"Osteoclast formation and differentiation: an overview","volume":"59","author":"Soysa","year":"2012","journal-title":"J. Med. Dent Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1210\/edrv-13-1-66","article-title":"Modulation of osteoclast differentiation","volume":"13","author":"Suda","year":"1992","journal-title":"Endocr. Rev."},{"key":"B37","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s11657-013-0137-0","article-title":"Osteoporosis in the European Union: a compendium of country-specific reports","volume":"8","author":"Svedbom","year":"2013","journal-title":"Arch. Osteoporos."},{"key":"B38","doi-asserted-by":"publisher","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. Cel"},{"key":"B39","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1002\/jbmr.3640","article-title":"The cost of osteoporosis, osteopenia, and associated fractures in Australia in 2017","volume":"34","author":"Tatangelo","year":"2019","journal-title":"J. Bone Miner Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/360741a0","article-title":"Bone and haematopoietic defects in mice lacking c-fos","volume":"360","author":"Wang","year":"1992","journal-title":"Nature"},{"key":"B41","doi-asserted-by":"publisher","first-page":"96","DOI":"10.14715\/cmb\/2019.65.6.16","article-title":"Sesamolin exerts anti-proliferative and apoptotic effect on human colorectal cancer cells via inhibition of JAK2\/STAT3 signaling pathway","volume":"65","author":"Wu","year":"2019","journal-title":"Cel Mol Biol (Noisy-le-grand)"},{"key":"B42","doi-asserted-by":"publisher","first-page":"4426","DOI":"10.3390\/molecules24244426","article-title":"Anti-inflammatory and anticancer properties of bioactive compounds from Sesamum indicum L.-A review","volume":"24","author":"Wu","year":"2019","journal-title":"Molecules"},{"key":"B43","doi-asserted-by":"publisher","first-page":"336","DOI":"10.4248\/br201304004","article-title":"Mice deficient in NF-\u03baB p50 and p52 or RANK have defective growth plate formation and post-natal dwarfism","volume":"1","author":"Xing","year":"2013","journal-title":"Bone Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"596789","DOI":"10.1155\/2015\/596789","article-title":"Proteomic analysis of estrogen-mediated signal transduction in osteoclasts formation","volume":"2015","author":"Xiong","year":"2015","journal-title":"Biomed. Res. Int."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.664697\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T12:16:06Z","timestamp":1623672966000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.664697\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,14]]},"references-count":44,"alternative-id":["10.3389\/fphar.2021.664697"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.664697","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,14]]},"article-number":"664697"}}