{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:41:05Z","timestamp":1780591265875,"version":"3.54.1"},"reference-count":50,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T00:00:00Z","timestamp":1758931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hakkaisan Brewery Co., Ltd., Niigata, Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: With the aging of the population, the number of patients with osteoporosis is increasing worldwide. Osteoporosis results from an imbalance in bone remodeling by osteoblasts and osteoclasts. This study investigated the effects of sake lees and rice koji, traditional Japanese rice-fermented products, on bone metabolism. Methods: Both sake lees extract and rice koji extract increased alkaline phosphatase (ALP) activity, extracellular collagen accumulation, and mineralization of MC3T3-E1 cells. In addition, the intracellular protein levels of Hsp47 and Sec23IP, which are required for collagen maturation and secretion, respectively, were increased during the differentiation. On the other hand, both extracts significantly inhibited osteoclastic differentiation. Furthermore, the effects of freeze-dried sake lees or rice koji extract on osteoporotic bones were examined using twelve-week-old female C3H\/HeJ ovariectomized (OVX) mice. Results: The groups of mice fed 20% or 40% freeze-dried sake lees showed significant suppression of the loss in bone volume fraction (BV\/TV) and trabecular volume (Tb.V) compared with those fed a normal diet as well as the 40% freeze-dried sake lees-fed group reduced in the loss of trabecular thickness (Tb.Th). Similarly, the rice koji extract-treated mice showed significant inhibition of the loss in BV\/TV, Tb.V, and even trabecular number (Tb.N.). Folic acid and S-adenosylmethionine (SAM), which have been reported to be present in sake lees, promoted extracellular collagen production by osteoblasts. Conclusions: In OVX mice, the intake of freeze-dried sake lees or rice koji extract was associated with the attenuation of trabecular bone loss, suggesting potential beneficial effects on bone metabolism.<\/jats:p>","DOI":"10.3390\/nu17193077","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T11:40:52Z","timestamp":1759146052000},"page":"3077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Freeze-Dried Sake Lees and Rice Koji Extract on Osteoporosis in a Postmenopausal Mouse Model"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6501-2198","authenticated-orcid":false,"given":"Jorge","family":"S\u00e1ez-Chand\u00eda","sequence":"first","affiliation":[{"name":"Division of Oral and Maxillofacial Radiology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan"},{"name":"Division of Dental Pharmacology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan"},{"name":"Faculty of Dentistry, Universidad de los Andes, Santiago 7580009, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7719-0007","authenticated-orcid":false,"given":"Stephanny","family":"Castillo-Quispe","sequence":"additional","affiliation":[{"name":"Division of Dental Pharmacology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan"},{"name":"Division of Oral Biochemistry, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3519-9561","authenticated-orcid":false,"given":"Keiichiro","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Division of Oral Physiology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan"},{"name":"Sakeology Center, Niigata University, Niigata 950-2181, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4427-193X","authenticated-orcid":false,"given":"Atsushi","family":"Kurahashi","sequence":"additional","affiliation":[{"name":"Hakkaisan Brewery Co., Ltd., Minamiuonuma 949-7112, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Kodaira","sequence":"additional","affiliation":[{"name":"Hakkaisan Brewery Co., Ltd., Minamiuonuma 949-7112, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Aihara","sequence":"additional","affiliation":[{"name":"Food Research Center, Niigata Agricultural Research Institute, Kamo 959-1381, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoko","family":"Suzuki-Barrera","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, Universidad de los Andes, Santiago 7580009, Chile"},{"name":"Division of Anatomy and Cell Biology of the Hard Tissue, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7988-6435","authenticated-orcid":false,"given":"Masaru","family":"Kaku","sequence":"additional","affiliation":[{"name":"Division of Bio-Prosthodontics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9263-3937","authenticated-orcid":false,"given":"Yoshikazu","family":"Mikami","sequence":"additional","affiliation":[{"name":"Division of Microscopic Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Terunuma","sequence":"additional","affiliation":[{"name":"Division of Oral Biochemistry, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4797-6874","authenticated-orcid":false,"given":"Kensuke","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Division of Oral Physiology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8421-0253","authenticated-orcid":false,"given":"Takafumi","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Division of Oral and Maxillofacial Radiology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makio","family":"Saeki","sequence":"additional","affiliation":[{"name":"Division of Dental Pharmacology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshito","family":"Kakihara","sequence":"additional","affiliation":[{"name":"Division of Dental Pharmacology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan"},{"name":"Sakeology Center, Niigata University, Niigata 950-2181, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Florencio-Silva, R., Sasso, G.R.D.S., Sasso-Cerri, E., Sim\u00f5es, M.J., and Cerri, P.S. 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