{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:05:12Z","timestamp":1790287512499,"version":"4.1.0"},"reference-count":111,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Zurich","award":["42870"],"award-info":[{"award-number":["42870"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bacterium-triggered carious lesions implicate dental hard tissue destruction and the simultaneous initiation of regenerative events comprising dental stem cell activation. Streptococcus mutans (S. mutans) is a prominent pathogen of the oral cavity and the principal cause of caries. S. mutans generates complex products involved in interbacterial interactions, including Mutanobactin-D (Mub-D), which belongs to a group of non-ribosomal cyclic lipopeptides. In the present study, we aimed to analyse the potential role of the synthetic Mub-D peptide in cell populations involved in tissue regenerative processes. To this end, we assessed the in vitro effects of Mub-D in human dental pulp stem cells (hDPSCs) and human bone marrow stem cells (hBMSCs). Our data demonstrated a concentration-dependent effect of Mub-D on their viability and a significant increase in their proliferation and osteogenic\/odontogenic differentiation. These events were associated with specific changes in gene expression, where CCDN-1, RUNX-2, OSX, OCN, DMP-1, DSPP, and BMP-2 genes were upregulated. The ability of Mub-D to modulate the osteogenic\/odontogenic differentiation of both hDPSCs and hBMSCs and considerably enhance mineralisation in a controlled and concentration-dependent manner opens new perspectives for stem cell-based regenerative approaches in the clinics.<\/jats:p>","DOI":"10.3390\/ijms26031144","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T10:44:30Z","timestamp":1738061070000},"page":"1144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mutanobactin-D, a Streptococcus mutans Non-Ribosomal Cyclic Lipopeptide, Induces Osteogenic\/Odontogenic Differentiation of Human Dental Pulp Stem Cells and Human Bone Marrow Stem Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"Sandra","family":"Nikolic","sequence":"first","affiliation":[{"name":"Orofacial Development and Regeneration, Institute of Oral Biology, Faculty of Medicine, Centre of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9168-2240","authenticated-orcid":false,"given":"Giuseppe","family":"Alastra","sequence":"additional","affiliation":[{"name":"Orofacial Development and Regeneration, Institute of Oral Biology, Faculty of Medicine, Centre of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland"},{"name":"Department of Veterinary Medical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8900-4734","authenticated-orcid":false,"given":"Felix","family":"Pultar","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Z\u00fcrich, 8093 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1478-743X","authenticated-orcid":false,"given":"Lukas","family":"L\u00fcthy","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Z\u00fcrich, 8093 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Stadlinger","sequence":"additional","affiliation":[{"name":"Clinic of Cranio-Maxillofacial and Oral Surgery, University of Zurich, 8032 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1472-490X","authenticated-orcid":false,"given":"Erick M.","family":"Carreira","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Z\u00fcrich, 8093 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac Maximiliano","family":"Bugueno","sequence":"additional","affiliation":[{"name":"Orofacial Development and Regeneration, Institute of Oral Biology, Faculty of Medicine, Centre of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9812-9982","authenticated-orcid":false,"given":"Thimios A.","family":"Mitsiadis","sequence":"additional","affiliation":[{"name":"Orofacial Development and Regeneration, Institute of Oral Biology, Faculty of Medicine, Centre of Dental Medicine, University of Zurich, 8032 Zurich, Switzerland"},{"name":"Foundation for Research and Technology\u2014Hellas (FORTH), University of Crete, 700 13 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/ismej.2012.174","article-title":"The Subgingival Microbiome in Health and Periodontitis and Its Relationship with Community Biomass and Inflammation","volume":"7","author":"Abusleme","year":"2013","journal-title":"ISME J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41579-023-00963-6","article-title":"The Oral Microbiome: Diversity, Biogeography and Human Health","volume":"22","author":"Baker","year":"2024","journal-title":"Nat. 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