{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T21:10:44Z","timestamp":1776373844242,"version":"3.51.2"},"reference-count":33,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kansai Medical University Molecular Imaging Center of Diseases"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoporosis is a common bone disease, particularly in menopausal women. Herein, we screened four Kampo medicines (Unkeito (UKT), Kamishoyosan (KSS), Kamikihito (KKT), and Ninjinyoeito (NYT)), frequently used to treat menopausal syndromes, for their effects on receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation in RAW 264 cells. Considering that UKT exhibited the most potent effect, we examined its effect on RANKL-induced osteoclastogenesis, the induction of osteoclast apoptosis, and the mechanisms underlying its effects. UKT inhibits RANKL-induced osteoclast differentiation in the early stage and decreases osteoclast-related genes, including tartrate-resistant acid phosphatase (Trap), dendritic cell-specific transmembrane protein (Dcstamp), matrix metalloproteinase-9 (Mmp9), and cathepsin K (Ctsk). Specifically, UKT inhibits the nuclear factor of activated T cells 1 (NFATc1), which is essential for osteoclastogenesis. UKT increases Bcl6, which antagonizes NFATc1 and Dc-stamp, thereby blocking the progression of osteoclasts to maturation. UKT also decreased nuclear translocation by downregulating the activity of p65\/NF-\u03baB. In addition, UKT enhances mononuclear osteoclast apoptosis via activation of caspase-3. Herein, we demonstrate that UKT suppresses RANKL-mediated osteoclastogenesis via the Blimp1\u2013Bcl6 and NF-\u03baB signaling pathways and enhances mononuclear osteoclast apoptosis. Furthermore, UKT prevents bone loss in OVX mice. Thus, UKT might be a potential therapeutic agent for postmenopausal osteoporosis.<\/jats:p>","DOI":"10.3390\/ijms23147814","type":"journal-article","created":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T22:57:06Z","timestamp":1658098626000},"page":"7814","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Unkeito Suppresses RANKL-Mediated Osteoclastogenesis via the Blimp1\u2013Bcl6 and NF-\u03baB Signaling Pathways and Enhancing Osteoclast Apoptosis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7390-8488","authenticated-orcid":false,"given":"Ke","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Hygiene and Public Health, Kansai Medical University, 2-5-1 Shin-machi, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7085-4832","authenticated-orcid":false,"given":"Yuki","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Hygiene and Public Health, Kansai Medical University, 2-5-1 Shin-machi, Hirakata 573-1010, Japan"},{"name":"Regenerative Research Center for Intractable Diseases, Kansai Medical University, 2-5-1 Shin-machi, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1797-3509","authenticated-orcid":false,"given":"Seiji","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Hygiene and Public Health, Kansai Medical University, 2-5-1 Shin-machi, Hirakata 573-1010, Japan"},{"name":"Regenerative Research Center for Intractable Diseases, Kansai Medical University, 2-5-1 Shin-machi, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takaki","family":"Shimono","sequence":"additional","affiliation":[{"name":"Department of Hygiene and Public Health, Kansai Medical University, 2-5-1 Shin-machi, Hirakata 573-1010, Japan"},{"name":"Regenerative Research Center for Intractable Diseases, Kansai Medical University, 2-5-1 Shin-machi, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anh Tuan","family":"Dang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"},{"name":"Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuaki","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan"},{"name":"Department of Oral Rehabilitation and Implantology, Okayama University Hospital, Okayama 700-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshimasa","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Department of Hygiene and Public Health, Kansai Medical University, 2-5-1 Shin-machi, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,15]]},"reference":[{"key":"ref_1","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. 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