{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:16:19Z","timestamp":1785417379669,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Asahi Groups Holdings, Ltd."},{"id":[{"id":"https:\/\/ror.org\/014aeyd41","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Inoue Enryou Memorial Foundation of Toyo University"},{"id":[{"id":"https:\/\/ror.org\/059d6yn51","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoporosis is characterized by reductions in bone mineral density (BMD) and bone quality. While gut-derived signaling has been increasingly studied in relation to BMD, its contribution to molecular factors associated with bone quality remains less defined. Here, we investigated whether a heat-inactivated, freeze-dried, non-viable preparation of Levilactobacillus brevis AS-1 modulates intestinal epithelial-like cells and thereby promotes lysyl oxidase (LOX), a key enzyme involved in collagen cross-linking. Caco-2 cells were treated using 1 mM sodium butyrate and subsequently stimulated with 100 \u03bcg\/mL L. brevis AS-1. Supernatants were collected and applied to MG63 cells. Cytokine mRNA expression in Caco-2 cells and LOX responses in MG63 cells were analyzed by qRT-PCR, and bone morphogenetic protein (BMP-1) and transforming growth factor-\u03b2 (TGF-\u03b2)1 protein levels in the supernatant were measured by ELISA. L. brevis AS-1 stimulation up-regulated BMP-1 and TGF-\u03b21 mRNA expression in SB-treated Caco-2 cells and increased BMP-1 protein secretion into the supernatant. LOX mRNA expression and total LOX activity were increased in MG63 cells treated with the conditioned supernatant, and inhibition of BMP-1\/procollagen C-proteinase activity (UK383367) attenuated LOX mRNA induction. Collectively, these results suggest that L. brevis AS-1 stimulates intestinal epithelial-like cells to secrete BMP-1, which in turn promotes LOX mRNA expression in osteoblast precursor cells. This in vitro mechanism supports the concept of gut\u2013bone crosstalk regulating molecular factors associated with bone quality.<\/jats:p>","DOI":"10.3390\/ijms27073156","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T08:09:18Z","timestamp":1774944558000},"page":"3156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intestinal Epithelial-like Cells Stimulated by a Functional Food Ingredient Promote Lysyl Oxidase (LOX) Expression in Osteoblast Precursor Cells via BMP-1 Secretion"],"prefix":"10.3390","volume":"27","author":[{"given":"Naoki","family":"Fujimoto","sequence":"first","affiliation":[{"name":"Graduate School of Health and Sports Sciences, Toyo University, Tokyo 115-8650, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Graduate School of Health and Sports Sciences, Toyo University, Tokyo 115-8650, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9490-3424","authenticated-orcid":false,"given":"Tomohiro","family":"Yano","sequence":"additional","affiliation":[{"name":"Graduate School of Health and Sports Sciences, Toyo University, Tokyo 115-8650, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Sakata","sequence":"additional","affiliation":[{"name":"Asahi Quality & Innovations, Ltd., Moriya-Shi 302-0106, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Ito","sequence":"additional","affiliation":[{"name":"Asahi Quality & Innovations, Ltd., Moriya-Shi 302-0106, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3669-3932","authenticated-orcid":false,"given":"Tatsuya","family":"Ishida","sequence":"additional","affiliation":[{"name":"Graduate School of Health and Sports Sciences, Toyo University, Tokyo 115-8650, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Saito, M., and Marumo, K. 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