{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:17:30Z","timestamp":1785406650429,"version":"3.56.0"},"reference-count":59,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy Cluj-Napoca"},{"id":[{"id":"https:\/\/ror.org\/051h0cw83","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Periodontal ligament mesenchymal stem cells (PL-MSCs) are vital for both periodontal regeneration and alveolar bone maintenance, including their turnover during orthodontic therapy. Chronic periodontal inflammation, mainly caused by Gram-negative bacterial lipopolysaccharides (LPS), interferes with osteogenic differentiation and leads to bone loss. Increasing evidence indicates that long non-coding RNAs (lncRNAs) link inflammatory signaling to osteogenic regulation, but their specific role in LPS-driven modulation of PL-MSC osteogenesis is not well understood. The aim of this study was to assess the effects of LPS from two bacterial strains on PL-MSCs differentiation. Human PL-MSCs were cultured under standard stem cell or osteogenic conditions and treated with LPS from Escherichia coli or Porphyromonas gingivalis. Mineralization was assessed using Alizarin Red staining. Osteogenic differentiation was evaluated through immunocytochemical analysis of osteopontin, collagen type 1, osteocalcin, osteonectin, and dentin matrix protein-1 (DMP-1). Expression levels of lncRNAs growth arrest-specific transcript 5 (GAS5), Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), maternally expressed gene 3 (MEG3) and Nuclear Enriched Abundant Transcript 1 (NEAT1) were measured by real-time PCR at 6, 24 and 48 h of LPS exposure. Exposure to E. coli LPS significantly inhibited extracellular matrix mineralization and decreased the expression of key osteogenic markers, indicating impaired osteoblast maturation. In contrast, P. gingivalis LPS caused a partial, dysregulated osteogenic response, marked by increased expression of osteopontin, osteonectin, and dentin matrix protein-1 (DMP-1), but without complete differentiation. LPS types altered lncRNA expression profiles, suggesting that non-coding regulatory networks are involved in inflammation-induced osteogenic dysregulation. Multivariate analyses showed decreased expression of GAS5, MEG3, and MALAT1 in the LPS vs. CTR comparison, decreased COL1A1 in LPS-PG vs. CTR, and increased OSTEOPONTIN in LPS vs. CTR. Differentiation was significantly associated with reduced expression of XIST and NEAT1. Time exerted significant effects on GAS5, MEG3, XIST, and MALAT1, with lower expression at 48 h compared with 6 h, and on COL1A1, which was significantly reduced at both 24 h and 48 h relative to 6 h. Bacterial LPS disrupt osteogenic differentiation of PL-MSCs depending on the species, affecting matrix formation, mineralization, and lncRNA expression. These findings highlight lncRNA-mediated communication between inflammatory signals and osteogenic pathways, providing new insights into the molecular mechanisms of inflammation-related bone remodeling in periodontal disease and orthodontic movements. Targeting lncRNA-regulated pathways could be a promising strategy to enhance periodontal regeneration during inflammation and also ensure optimum outcomes in orthodontic therapy.<\/jats:p>","DOI":"10.3390\/ijms27115006","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"5006","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Effects of Escherichia coli vs. Porphyromonas gingivalis Lipopolysaccharides on Osteogenic Differentiation and the Expression of lncRNAs in Periodontal Ligament Stem Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8819-289X","authenticated-orcid":false,"given":"Tudor-Sergiu","family":"Suciu","sequence":"first","affiliation":[{"name":"Department of Orthodontics and Dentofacial Orthopedics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400083 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simion","family":"Bran","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery and Implantology, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400029 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5828-1325","authenticated-orcid":false,"given":"Ioana","family":"Berindan-Neagoe","sequence":"additional","affiliation":[{"name":"Department of Genomics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania"},{"name":"Doctoral School, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400029 Cluj-Napoca, Romania"},{"name":"Academy of Medical Sciences, 030167 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3926-5423","authenticated-orcid":false,"given":"Lajos","family":"Raduly","sequence":"additional","affiliation":[{"name":"Department of Genomics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana","family":"Zanoaga","sequence":"additional","affiliation":[{"name":"Department of Genomics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Budisan","sequence":"additional","affiliation":[{"name":"Department of Genomics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Nutu","sequence":"additional","affiliation":[{"name":"Department of Genomics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9270-8529","authenticated-orcid":false,"given":"Olga","family":"Soritau","sequence":"additional","affiliation":[{"name":"Department of Genomics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6112-0223","authenticated-orcid":false,"given":"Stefan","family":"Strilciuc","sequence":"additional","affiliation":[{"name":"Department of Genomics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Leucu\u021ba","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics and Biostatistics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Fe\u0219til\u0103","sequence":"additional","affiliation":[{"name":"Department of Orthodontics and Dentofacial Orthopedics, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400083 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8800-4935","authenticated-orcid":false,"given":"Oana","family":"Alm\u0103\u0219an","sequence":"additional","affiliation":[{"name":"Department of Prosthetics and Dental Materials, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra Iulia","family":"Aghiorghiesei","sequence":"additional","affiliation":[{"name":"Department of Prosthetics and Dental Materials, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"B\u0103ciu\u021b","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Surgery and Implantology, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400029 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1186\/s13287-024-04003-9","article-title":"Dental stem cell dynamics in periodontal ligament regeneration: From mechanism to 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