Primary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address t...Primary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address this, RNA sequencing was used to generate transcriptomes of furcal bone from infraoccluded(n = 7) and non-infraoccluded(n = 9) primary second molars, all without succeeding biscuspids. Of the 18 529 expressed genes, 432(2.3%) genes were differentially expressed between the two groups(false discovery rate < 0.05). Hierarchical clustering and principal component analysis showed clear separation in gene expression between infraoccluded and non-infraoccluded samples. Pathway analyses indicated that molar ankylosis is associated with the expression of genes consistent with the cellular inflammatory response and epithelial cell turnover. Independent validation using six expressed genes by immunohistochemical analysis demonstrated that the corresponding proteins are strongly expressed in the developing molar tooth germ, in particular the dental follicle and inner enamel epithelium. The descendants of these structures include the periodontal ligament, cementum, bone and epithelial rests of Malassez;tissues that are central to the ankylotic process.We therefore propose that ankylosis involves an increased inflammatory response associated with disruptions to the developmental remnants of the dental follicle and epithelial rests of Malassez.展开更多
Pten controls a signaling axis that is implicated to regulate cell proliferation,growth,survival,migration,and metabolism.The molecular mechanisms underlying the specificity of Pten responses to such diverse cellular ...Pten controls a signaling axis that is implicated to regulate cell proliferation,growth,survival,migration,and metabolism.The molecular mechanisms underlying the specificity of Pten responses to such diverse cellular functions are currently poorly understood.Herewe report the control of Pten activity and signaling specificity during the cell cycle by Ndfip1 regulation of Pten spatial distribution.Genetic deletion of Ndfip1 resulted in a loss of Pten nuclear compartmentalization and increased cell proliferation,despite cytoplasmic Pten remaining active in regulating PI3K/Akt signaling.Cells lacking nuclear Pten were found to have dysregulated levels of Plk1 and cyclin D1 that could drive cell proliferation.In vivo,transgene expression of Ndfip1 in the developing brain increased nuclear Pten and lengthened the cell cycle of neuronal progenitors,resulting in microencephaly.Our results show that local partitioning of Pten from the cytoplasm to the nucleus represents a key mechanism contributing to the specificity of Pten signaling during cell proliferation.展开更多
基金supported by a grant from the Australian Society of Orthodontists Foundation for Research and Education(ASOFRE).
文摘Primary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address this, RNA sequencing was used to generate transcriptomes of furcal bone from infraoccluded(n = 7) and non-infraoccluded(n = 9) primary second molars, all without succeeding biscuspids. Of the 18 529 expressed genes, 432(2.3%) genes were differentially expressed between the two groups(false discovery rate < 0.05). Hierarchical clustering and principal component analysis showed clear separation in gene expression between infraoccluded and non-infraoccluded samples. Pathway analyses indicated that molar ankylosis is associated with the expression of genes consistent with the cellular inflammatory response and epithelial cell turnover. Independent validation using six expressed genes by immunohistochemical analysis demonstrated that the corresponding proteins are strongly expressed in the developing molar tooth germ, in particular the dental follicle and inner enamel epithelium. The descendants of these structures include the periodontal ligament, cementum, bone and epithelial rests of Malassez;tissues that are central to the ankylotic process.We therefore propose that ankylosis involves an increased inflammatory response associated with disruptions to the developmental remnants of the dental follicle and epithelial rests of Malassez.
基金This work was supported by the Australia National Health and Medical Research Council through Program and Project Grants(grant numbers 569575 and 1066895)the Victorian Government through the Operational Infrastructure Scheme.
文摘Pten controls a signaling axis that is implicated to regulate cell proliferation,growth,survival,migration,and metabolism.The molecular mechanisms underlying the specificity of Pten responses to such diverse cellular functions are currently poorly understood.Herewe report the control of Pten activity and signaling specificity during the cell cycle by Ndfip1 regulation of Pten spatial distribution.Genetic deletion of Ndfip1 resulted in a loss of Pten nuclear compartmentalization and increased cell proliferation,despite cytoplasmic Pten remaining active in regulating PI3K/Akt signaling.Cells lacking nuclear Pten were found to have dysregulated levels of Plk1 and cyclin D1 that could drive cell proliferation.In vivo,transgene expression of Ndfip1 in the developing brain increased nuclear Pten and lengthened the cell cycle of neuronal progenitors,resulting in microencephaly.Our results show that local partitioning of Pten from the cytoplasm to the nucleus represents a key mechanism contributing to the specificity of Pten signaling during cell proliferation.
