Impact of Amelogenesis Imperfecta on Junctional Epithelium Structure and Function
The junctional epithelium, which lines the inner gingival surface, seals the gingival sulcus to block the infiltration of food debris and pathogens. The junctional epithelium is derived from the reduced enamel epithelium, consisting of late developmental stage ameloblasts and accessory cells. No pri...
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2025-07-01
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| author | Kevin Lin Jake Ngu Susu Uyen Le Yan Zhang |
| author_facet | Kevin Lin Jake Ngu Susu Uyen Le Yan Zhang |
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| description | The junctional epithelium, which lines the inner gingival surface, seals the gingival sulcus to block the infiltration of food debris and pathogens. The junctional epithelium is derived from the reduced enamel epithelium, consisting of late developmental stage ameloblasts and accessory cells. No prior studies have investigated whether defective ameloblast differentiation or enamel matrix formation affects junctional epithelium anatomy or function. Here, we examined the junctional epithelium in mice exhibiting amelogenesis imperfecta due to loss-of-function mutations in the major enamel matrix protein amelogenin (<i>Amelx</i><sup>−/−</sup>) or the critical enamel matrix protease KLK4 (<i>Klk4</i><sup>−/−</sup>). Histological analyses demonstrated altered morphology and cell layer thickness of the junctional epithelium in <i>Amelx</i><sup>−/−</sup> and <i>Klk4</i><sup>−/−</sup> mice as compared to <i>wt</i>. Immunohistochemistry revealed reduced ODAM, laminin 5, and integrin α6, all of which are critical for the adhesion of the junctional epithelium to the enamel in <i>Amelx</i><sup>−/−</sup> and <i>Klk4</i><sup>−/−</sup> mice. Furthermore, we observed altered cell–cell adhesion and increased permeability of Dextran-GFP through the mutants’ junctional epithelium, indicating defective barrier function. Reduced β-catenin and Ki67 at the base of the junctional epithelium in mutants suggest impaired mitotic activity and reduced capacity to replenish continuously desquamated epithelium. These findings highlight the essential role of normal amelogenesis in maintaining junctional epithelium homeostasis. |
| format | Article |
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| spelling | doaj-art-cfefad0c513640eb82e6ebf62d1df9cb2025-07-25T13:15:11ZengMDPI AGBiology2079-77372025-07-0114785310.3390/biology14070853Impact of Amelogenesis Imperfecta on Junctional Epithelium Structure and FunctionKevin Lin0Jake Ngu1Susu Uyen Le2Yan Zhang3Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USADepartment of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USADepartment of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USADepartment of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA 94143, USAThe junctional epithelium, which lines the inner gingival surface, seals the gingival sulcus to block the infiltration of food debris and pathogens. The junctional epithelium is derived from the reduced enamel epithelium, consisting of late developmental stage ameloblasts and accessory cells. No prior studies have investigated whether defective ameloblast differentiation or enamel matrix formation affects junctional epithelium anatomy or function. Here, we examined the junctional epithelium in mice exhibiting amelogenesis imperfecta due to loss-of-function mutations in the major enamel matrix protein amelogenin (<i>Amelx</i><sup>−/−</sup>) or the critical enamel matrix protease KLK4 (<i>Klk4</i><sup>−/−</sup>). Histological analyses demonstrated altered morphology and cell layer thickness of the junctional epithelium in <i>Amelx</i><sup>−/−</sup> and <i>Klk4</i><sup>−/−</sup> mice as compared to <i>wt</i>. Immunohistochemistry revealed reduced ODAM, laminin 5, and integrin α6, all of which are critical for the adhesion of the junctional epithelium to the enamel in <i>Amelx</i><sup>−/−</sup> and <i>Klk4</i><sup>−/−</sup> mice. Furthermore, we observed altered cell–cell adhesion and increased permeability of Dextran-GFP through the mutants’ junctional epithelium, indicating defective barrier function. Reduced β-catenin and Ki67 at the base of the junctional epithelium in mutants suggest impaired mitotic activity and reduced capacity to replenish continuously desquamated epithelium. These findings highlight the essential role of normal amelogenesis in maintaining junctional epithelium homeostasis.https://www.mdpi.com/2079-7737/14/7/853ameloblastsenamel matrix formationamelogenesis imperfectathe junctional epitheliuminternal basal laminaepithelium barrier |
| spellingShingle | Kevin Lin Jake Ngu Susu Uyen Le Yan Zhang Impact of Amelogenesis Imperfecta on Junctional Epithelium Structure and Function Biology ameloblasts enamel matrix formation amelogenesis imperfecta the junctional epithelium internal basal lamina epithelium barrier |
| title | Impact of Amelogenesis Imperfecta on Junctional Epithelium Structure and Function |
| title_full | Impact of Amelogenesis Imperfecta on Junctional Epithelium Structure and Function |
| title_fullStr | Impact of Amelogenesis Imperfecta on Junctional Epithelium Structure and Function |
| title_full_unstemmed | Impact of Amelogenesis Imperfecta on Junctional Epithelium Structure and Function |
| title_short | Impact of Amelogenesis Imperfecta on Junctional Epithelium Structure and Function |
| title_sort | impact of amelogenesis imperfecta on junctional epithelium structure and function |
| topic | ameloblasts enamel matrix formation amelogenesis imperfecta the junctional epithelium internal basal lamina epithelium barrier |
| url | https://www.mdpi.com/2079-7737/14/7/853 |
| work_keys_str_mv | AT kevinlin impactofamelogenesisimperfectaonjunctionalepitheliumstructureandfunction AT jakengu impactofamelogenesisimperfectaonjunctionalepitheliumstructureandfunction AT susuuyenle impactofamelogenesisimperfectaonjunctionalepitheliumstructureandfunction AT yanzhang impactofamelogenesisimperfectaonjunctionalepitheliumstructureandfunction |