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DGI\u2010II, a hereditary dental disorder caused by\n                      <jats:italic>dentine sialophosphoprotein (Dspp)<\/jats:italic>\n                      gene mutations, results in fragile, discoloured teeth susceptible to wear and decay. This study investigates the structural alterations in the dentine matrix induced by mutant DSPP and the underlying molecular mechanisms. Furthermore, we evaluated a therapeutic strategy combining nanofibrous substrates with molecular activation of the Wnt5a\u2010Cdc42 pathway, aiming to mitigate these structural defects and restore dentine integrity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>\n                      A maxillary first premolar extracted from a patient with dentinogenesis imperfecta type II (DGI\u2010II) carrying a known\n                      <jats:italic>DSPP<\/jats:italic>\n                      frameshift mutation was analysed using micro\u2010computed tomography and scanning electron microscopy. MDPC\u201023 mouse dental pulp pre\u2010odontoblasts were cultured in\u00a0vitro on electrospun nanofibrous scaffolds with tunable fibre diameters.\n                      <jats:italic>Dspp<\/jats:italic>\n                      expression was silenced to investigate its regulatory role in cell\u2013cell contact formation, while the Wnt5a\u2010Cdc42 pathway was activated via recombinant Wnt5a protein and a small molecule. Data were analysed using Student's\n                      <jats:italic>t<\/jats:italic>\n                      \u2010test or one\u2010way ANOVA with a significance threshold of\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Decalcified or freeze\u2010fractured samples exhibited thick fibres, sparse dentinal tubules, and a disorganised, non\u2010layered dentine matrix, indicating that disrupted cell\u2013cell junctions impair directional appositional dentine formation. Silencing\n                      <jats:italic>Dspp<\/jats:italic>\n                      expression in dental pulp cells led to reduced expression of junctional proteins, Zona occludens\u20101 (ZO\u20101) and Connexin43 (Cx43), which are essential for vectorial matrix apposition. Modulating fibre thickness and activating the Wnt5a\u2010Cdc42 signalling axis restored both the expression and cellular localisation of ZO\u20101 and Cx43, thereby re\u2010establishing cell\u2013cell junctions and paracellular permeability in\n                      <jats:italic>Dspp<\/jats:italic>\n                      \u2010silenced dental pulp cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The results provide evidence that\n                      <jats:italic>Dspp<\/jats:italic>\n                      contributes to the structural integrity of dentine by modulating ZO\u20101 and Cx43 expression and suggest that biomaterial and molecular interventions may offer supportive strategies to restore dentine structure and function in DGI\u2010affected teeth, though they do not address the underlying genetic defect.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70086","type":"journal-article","created":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T03:50:21Z","timestamp":1766634621000},"page":"656-668","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Restoring Cell\u2013Cell Junctions in\n                    <i>DSPP<\/i>\n                    \u2010Deficient Odontoblasts Through Nanofibrous Topography and Wnt5a\u2010Cdc42 Activation: A Laboratory Investigation"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7240-2592","authenticated-orcid":false,"given":"Jieun","family":"Bae","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, School of Dentistry and Dental Research Institute Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9399-2197","authenticated-orcid":false,"given":"Jung\u2010Wook","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, School of Dentistry and Dental Research Institute Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-1189","authenticated-orcid":false,"given":"Kyung Mi","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, School of Dentistry and Dental Research Institute Seoul National University  Seoul Republic of Korea"},{"name":"Department of Pharmacology &amp; Dental Therapeutics, School of Dentistry Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dental.2019.10.011"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-3-31"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13644"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0285217"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.5051\/jpis.2103760188"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12676"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/dj11040095"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.6b14283"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.2741\/e281"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/154411130401500103"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13885"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2010.353"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S217420"},{"key":"e_1_2_10_15_1","first-page":"338","article-title":"Tight Junctions in Differentiating Ameloblasts and Odontoblasts Differentially Express ZO\u20101, Occludin, and Claudin\u20101 in Early Odontogenesis of Rat Molars","volume":"277","author":"Jo\u00e3o S. 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