The Experts below are selected from a list of 1170 Experts worldwide ranked by ideXlab platform

Boyen Huang - One of the best experts on this subject based on the ideXlab platform.

  • loss of stemness emt and supernumerary tooth formation in CEBPB runx2 murine incisors
    Scientific Reports, 2018
    Co-Authors: Kazuyuki Saito, Boyen Huang, Katsu Takahashi, Honoka Kiso, Yumiko Togo, Hiroko Tsukamoto, Masakazu Asahara, Sayaka Mishima, Masaki Nagata, Machiko Iida
    Abstract:

    Adult CEBPB KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, CEBPB acts upstream of Sox2 to regulate stemness. In this study, CEBPB KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a CEBPB knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell line presented a similar expression pattern. Therefore, the EMT enabled disengaged odontogenic epithelial stem cells to develop supernumerary teeth. CEBPB and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin expression, and Decorin-positive staining in the periapical region, indicating their involvement in supernumerary tooth formation. CEBPB and Runx2 acted synergistically and played an important role in the formation of supernumerary teeth in adult incisors.

  • Loss of Stemness, EMT, and Supernumerary Tooth Formation in CEBPB −/− Runx2 +/− Murine Incisors
    Nature Publishing Group, 2018
    Co-Authors: Kazuyuki Saito, Boyen Huang, Katsu Takahashi, Honoka Kiso, Yumiko Togo, Hiroko Tsukamoto, Masakazu Asahara, Sayaka Mishima, Masaki Nagata, Machiko Iida
    Abstract:

    Abstract Adult CEBPB KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, CEBPB acts upstream of Sox2 to regulate stemness. In this study, CEBPB KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a CEBPB knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell line presented a similar expression pattern. Therefore, the EMT enabled disengaged odontogenic epithelial stem cells to develop supernumerary teeth. CEBPB and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin expression, and Decorin-positive staining in the periapical region, indicating their involvement in supernumerary tooth formation. CEBPB and Runx2 acted synergistically and played an important role in the formation of supernumerary teeth in adult incisors

  • prospective signs of cleidocranial dysplasia in CEBPB deficiency
    Journal of Biomedical Science, 2014
    Co-Authors: Boyen Huang, Katsu Takahashi, Ernest A Jennings, Pongthorn Pumtangon, Honoka Kiso, Yumiko Togo, Kazuyuki Saito, Manabu Sugai, Shizuo Akira
    Abstract:

    Although runt-related transcription factor 2 (RUNX2) has been considered a determinant of cleidocranial dysplasia (CCD), some CCD patients were free of RUNX2 mutations. CCAAT/enhancer-binding protein beta (CEBPB) is a key factor of Runx2 expression and our previous study has reported two CCD signs including hyperdontia and elongated coronoid process of the mandible in CEBPB deficient mice. Following that, this work aimed to conduct a case-control study of thoracic, zygomatic and masticatory muscular morphology to propose an association between musculoskeletal phenotypes and deficiency of CEBPB, using a sample of CEBPB-/-, CEBPB+/- and CEBPB+/+ adult mice. Somatic skeletons and skulls of mice were inspected with soft x-rays and micro-computed tomography (μCT), respectively. Zygomatic inclination was assessed using methods of coordinate geometry and trigonometric function on anatomic landmarks identified with μCT. Masseter and temporal muscles were collected and weighed. Expression of CEBPB was examined with a reverse transcriptase polymerase chain reaction (RT-PCR) technique. CEBPB-/- mice displayed hypoplastic clavicles, a narrow thoracic cage, and a downward tilted zygomatic arch (p < 0.001). Although CEBPB+/- mice did not show the phenotypes above (p = 0.357), a larger mass percentage of temporal muscles over masseter muscles was seen in CEBPB+/- littermates (p = 0.012). The mRNA expression of CEBPB was detected in the clavicle, the zygoma, the temporal muscle and the masseter muscle, respectively. Prospective signs of CCD were identified in mice with CEBPB deficiency. These could provide an additional aetiological factor of CCD. Succeeding investigation into interactions among CEBPB, Runx2 and musculoskeletal development is indicated.

  • phenotypes of ccaat enhancer binding protein beta deficiency hyperdontia and elongated coronoid process
    Oral Diseases, 2013
    Co-Authors: Boyen Huang, Katsu Takahashi, Honoka Kiso, Yumiko Togo, Kazuyuki Saito, Manabu Sugai, Shizuo Akira, Tomoko Sakatagoto, Hiroko Tsukamoto, Akira Shimizu
    Abstract:

    Objectives:  This investigation aimed to conduct a case-control study of mandibular morphology and dental anomalies to propose a relationship between mandibular/dental phenotypes and deficiency of CCAAT/enhancer-binding protein beta (CEBPB). Materials and methods:  Skulls of CEBPB(-/-) , CEBPB(+/-) and CEBPB(+/+) mice were inspected with micro-computed tomography. Mandibular morphology was assessed with a method of Euclidean distance matrix analysis. Results:  Elongation of the coronoid process was identified in CEBPB(+/-) (P ≤ 0.046) and CEBPB(-/-) 12-month-olds (P ≤ 0.028) but not in 14-day-olds (P ≥ 0.217) and 0-day-olds (P ≥ 0.189) of either genotype. Formation of supernumerary teeth in CEBPB(-/-) adult mice was demonstrated (χ(2 ) =( ) 6.00, df = 1, P = 0.014). Conclusions:  CEBPB deficiency was related to elongation of the coronoid process and formation of supernumerary teeth. The mandibular and dental phenotypes of CEBPB deficiency were unseen by the 14th day after birth. Future investigations into the influence of CEBPB on mandibular and dental development are needed.

Kazuyuki Saito - One of the best experts on this subject based on the ideXlab platform.

  • loss of stemness emt and supernumerary tooth formation in CEBPB runx2 murine incisors
    Scientific Reports, 2018
    Co-Authors: Kazuyuki Saito, Boyen Huang, Katsu Takahashi, Honoka Kiso, Yumiko Togo, Hiroko Tsukamoto, Masakazu Asahara, Sayaka Mishima, Masaki Nagata, Machiko Iida
    Abstract:

    Adult CEBPB KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, CEBPB acts upstream of Sox2 to regulate stemness. In this study, CEBPB KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a CEBPB knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell line presented a similar expression pattern. Therefore, the EMT enabled disengaged odontogenic epithelial stem cells to develop supernumerary teeth. CEBPB and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin expression, and Decorin-positive staining in the periapical region, indicating their involvement in supernumerary tooth formation. CEBPB and Runx2 acted synergistically and played an important role in the formation of supernumerary teeth in adult incisors.

  • Loss of Stemness, EMT, and Supernumerary Tooth Formation in CEBPB −/− Runx2 +/− Murine Incisors
    Nature Publishing Group, 2018
    Co-Authors: Kazuyuki Saito, Boyen Huang, Katsu Takahashi, Honoka Kiso, Yumiko Togo, Hiroko Tsukamoto, Masakazu Asahara, Sayaka Mishima, Masaki Nagata, Machiko Iida
    Abstract:

    Abstract Adult CEBPB KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, CEBPB acts upstream of Sox2 to regulate stemness. In this study, CEBPB KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a CEBPB knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell line presented a similar expression pattern. Therefore, the EMT enabled disengaged odontogenic epithelial stem cells to develop supernumerary teeth. CEBPB and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin expression, and Decorin-positive staining in the periapical region, indicating their involvement in supernumerary tooth formation. CEBPB and Runx2 acted synergistically and played an important role in the formation of supernumerary teeth in adult incisors

  • prospective signs of cleidocranial dysplasia in CEBPB deficiency
    Journal of Biomedical Science, 2014
    Co-Authors: Boyen Huang, Katsu Takahashi, Ernest A Jennings, Pongthorn Pumtangon, Honoka Kiso, Yumiko Togo, Kazuyuki Saito, Manabu Sugai, Shizuo Akira
    Abstract:

    Although runt-related transcription factor 2 (RUNX2) has been considered a determinant of cleidocranial dysplasia (CCD), some CCD patients were free of RUNX2 mutations. CCAAT/enhancer-binding protein beta (CEBPB) is a key factor of Runx2 expression and our previous study has reported two CCD signs including hyperdontia and elongated coronoid process of the mandible in CEBPB deficient mice. Following that, this work aimed to conduct a case-control study of thoracic, zygomatic and masticatory muscular morphology to propose an association between musculoskeletal phenotypes and deficiency of CEBPB, using a sample of CEBPB-/-, CEBPB+/- and CEBPB+/+ adult mice. Somatic skeletons and skulls of mice were inspected with soft x-rays and micro-computed tomography (μCT), respectively. Zygomatic inclination was assessed using methods of coordinate geometry and trigonometric function on anatomic landmarks identified with μCT. Masseter and temporal muscles were collected and weighed. Expression of CEBPB was examined with a reverse transcriptase polymerase chain reaction (RT-PCR) technique. CEBPB-/- mice displayed hypoplastic clavicles, a narrow thoracic cage, and a downward tilted zygomatic arch (p < 0.001). Although CEBPB+/- mice did not show the phenotypes above (p = 0.357), a larger mass percentage of temporal muscles over masseter muscles was seen in CEBPB+/- littermates (p = 0.012). The mRNA expression of CEBPB was detected in the clavicle, the zygoma, the temporal muscle and the masseter muscle, respectively. Prospective signs of CCD were identified in mice with CEBPB deficiency. These could provide an additional aetiological factor of CCD. Succeeding investigation into interactions among CEBPB, Runx2 and musculoskeletal development is indicated.

  • phenotypes of ccaat enhancer binding protein beta deficiency hyperdontia and elongated coronoid process
    Oral Diseases, 2013
    Co-Authors: Boyen Huang, Katsu Takahashi, Honoka Kiso, Yumiko Togo, Kazuyuki Saito, Manabu Sugai, Shizuo Akira, Tomoko Sakatagoto, Hiroko Tsukamoto, Akira Shimizu
    Abstract:

    Objectives:  This investigation aimed to conduct a case-control study of mandibular morphology and dental anomalies to propose a relationship between mandibular/dental phenotypes and deficiency of CCAAT/enhancer-binding protein beta (CEBPB). Materials and methods:  Skulls of CEBPB(-/-) , CEBPB(+/-) and CEBPB(+/+) mice were inspected with micro-computed tomography. Mandibular morphology was assessed with a method of Euclidean distance matrix analysis. Results:  Elongation of the coronoid process was identified in CEBPB(+/-) (P ≤ 0.046) and CEBPB(-/-) 12-month-olds (P ≤ 0.028) but not in 14-day-olds (P ≥ 0.217) and 0-day-olds (P ≥ 0.189) of either genotype. Formation of supernumerary teeth in CEBPB(-/-) adult mice was demonstrated (χ(2 ) =( ) 6.00, df = 1, P = 0.014). Conclusions:  CEBPB deficiency was related to elongation of the coronoid process and formation of supernumerary teeth. The mandibular and dental phenotypes of CEBPB deficiency were unseen by the 14th day after birth. Future investigations into the influence of CEBPB on mandibular and dental development are needed.

David J Steger - One of the best experts on this subject based on the ideXlab platform.

  • shared nucleotide flanks confer transcriptional competency to bzip core motifs
    Nucleic Acids Research, 2018
    Co-Authors: Daniel M Cohen, Heewoong Lim, Kyoungjae Won, David J Steger
    Abstract:

    Sequence-specific DNA binding recruits transcription factors (TFs) to the genome to regulate gene expression. Here, we perform high resolution mapping of CEBP proteins to determine how sequence dictates genomic occupancy. We demonstrate a fundamental difference between the sequence repertoire utilized by CEBPs in vivo versus the palindromic sequence preference reported by classical in vitro models, by identifying a palindromic motif at <1% of the genomic binding sites. On the native genome, CEBPs bind a diversity of related 10 bp sequences resulting from the fusion of degenerate and canonical half-sites. Altered DNA specificity of CEBPs in cells occurs through heterodimerization with other bZip TFs, and approximately 40% of CEBP-binding sites in primary human cells harbor motifs characteristic of CEBP heterodimers. In addition, we uncover an important role for sequence bias at core-motif-flanking bases for CEBPs and demonstrate that flanking bases regulate motif function across mammalian bZip TFs. Favorable flanking bases confer efficient TF occupancy and transcriptional activity, and DNA shape may explain how the flanks alter TF binding. Importantly, motif optimization within the 10-mer is strongly correlated with cell-type-independent recruitment of CEBPβ, providing key insight into how sequence sub-optimization affects genomic occupancy of widely expressed CEBPs across cell types.

  • shared nucleotide flanks confer transcriptional competency to bzip core motifs
    bioRxiv, 2018
    Co-Authors: Daniel M Cohen, David J Steger
    Abstract:

    Sequence-specific DNA binding recruits transcription factors (TFs) to the genome to regulate gene expression. Here, we perform high resolution mapping of CEBP proteins to determine how sequence dictates genomic occupancy. We demonstrate a fundamental difference between the sequence repertoire utilized by CEBPs in vivo versus the palindromic sequence preference reported by classical in vitro models, by identifying a palindromic motif at less than 1% of the genomic binding sites. On the native genome, CEBPs bind a diversity of related 10 bp sequences resulting from the fusion of degenerate and canonical half-sites. Altered DNA specificity of CEBPs in cells occurs through heterodimerization with other bZip TFs, and approximately 40% of CEBP-binding sites in primary human cells harbor motifs characteristic of CEBP heterodimers. In addition, we uncover an important role for sequence bias at core-motif-flanking bases for CEBPs and demonstrate that flanking bases regulate motif function across mammalian bZip TFs. Favorable flanking bases confer efficient TF occupancy and transcriptional activity, and DNA shape may explain how the flanks alter TF binding. Importantly, motif optimization within the 10-mer is strongly correlated with cell-type-independent recruitment of CEBPβ, providing key insight into how sequence sub-optimization affects genomic occupancy of widely expressed CEBPs across cell types.

Honoka Kiso - One of the best experts on this subject based on the ideXlab platform.

  • loss of stemness emt and supernumerary tooth formation in CEBPB runx2 murine incisors
    Scientific Reports, 2018
    Co-Authors: Kazuyuki Saito, Boyen Huang, Katsu Takahashi, Honoka Kiso, Yumiko Togo, Hiroko Tsukamoto, Masakazu Asahara, Sayaka Mishima, Masaki Nagata, Machiko Iida
    Abstract:

    Adult CEBPB KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, CEBPB acts upstream of Sox2 to regulate stemness. In this study, CEBPB KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a CEBPB knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell line presented a similar expression pattern. Therefore, the EMT enabled disengaged odontogenic epithelial stem cells to develop supernumerary teeth. CEBPB and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin expression, and Decorin-positive staining in the periapical region, indicating their involvement in supernumerary tooth formation. CEBPB and Runx2 acted synergistically and played an important role in the formation of supernumerary teeth in adult incisors.

  • Loss of Stemness, EMT, and Supernumerary Tooth Formation in CEBPB −/− Runx2 +/− Murine Incisors
    Nature Publishing Group, 2018
    Co-Authors: Kazuyuki Saito, Boyen Huang, Katsu Takahashi, Honoka Kiso, Yumiko Togo, Hiroko Tsukamoto, Masakazu Asahara, Sayaka Mishima, Masaki Nagata, Machiko Iida
    Abstract:

    Abstract Adult CEBPB KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, CEBPB acts upstream of Sox2 to regulate stemness. In this study, CEBPB KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a CEBPB knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell line presented a similar expression pattern. Therefore, the EMT enabled disengaged odontogenic epithelial stem cells to develop supernumerary teeth. CEBPB and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin expression, and Decorin-positive staining in the periapical region, indicating their involvement in supernumerary tooth formation. CEBPB and Runx2 acted synergistically and played an important role in the formation of supernumerary teeth in adult incisors

  • prospective signs of cleidocranial dysplasia in CEBPB deficiency
    Journal of Biomedical Science, 2014
    Co-Authors: Boyen Huang, Katsu Takahashi, Ernest A Jennings, Pongthorn Pumtangon, Honoka Kiso, Yumiko Togo, Kazuyuki Saito, Manabu Sugai, Shizuo Akira
    Abstract:

    Although runt-related transcription factor 2 (RUNX2) has been considered a determinant of cleidocranial dysplasia (CCD), some CCD patients were free of RUNX2 mutations. CCAAT/enhancer-binding protein beta (CEBPB) is a key factor of Runx2 expression and our previous study has reported two CCD signs including hyperdontia and elongated coronoid process of the mandible in CEBPB deficient mice. Following that, this work aimed to conduct a case-control study of thoracic, zygomatic and masticatory muscular morphology to propose an association between musculoskeletal phenotypes and deficiency of CEBPB, using a sample of CEBPB-/-, CEBPB+/- and CEBPB+/+ adult mice. Somatic skeletons and skulls of mice were inspected with soft x-rays and micro-computed tomography (μCT), respectively. Zygomatic inclination was assessed using methods of coordinate geometry and trigonometric function on anatomic landmarks identified with μCT. Masseter and temporal muscles were collected and weighed. Expression of CEBPB was examined with a reverse transcriptase polymerase chain reaction (RT-PCR) technique. CEBPB-/- mice displayed hypoplastic clavicles, a narrow thoracic cage, and a downward tilted zygomatic arch (p < 0.001). Although CEBPB+/- mice did not show the phenotypes above (p = 0.357), a larger mass percentage of temporal muscles over masseter muscles was seen in CEBPB+/- littermates (p = 0.012). The mRNA expression of CEBPB was detected in the clavicle, the zygoma, the temporal muscle and the masseter muscle, respectively. Prospective signs of CCD were identified in mice with CEBPB deficiency. These could provide an additional aetiological factor of CCD. Succeeding investigation into interactions among CEBPB, Runx2 and musculoskeletal development is indicated.

  • phenotypes of ccaat enhancer binding protein beta deficiency hyperdontia and elongated coronoid process
    Oral Diseases, 2013
    Co-Authors: Boyen Huang, Katsu Takahashi, Honoka Kiso, Yumiko Togo, Kazuyuki Saito, Manabu Sugai, Shizuo Akira, Tomoko Sakatagoto, Hiroko Tsukamoto, Akira Shimizu
    Abstract:

    Objectives:  This investigation aimed to conduct a case-control study of mandibular morphology and dental anomalies to propose a relationship between mandibular/dental phenotypes and deficiency of CCAAT/enhancer-binding protein beta (CEBPB). Materials and methods:  Skulls of CEBPB(-/-) , CEBPB(+/-) and CEBPB(+/+) mice were inspected with micro-computed tomography. Mandibular morphology was assessed with a method of Euclidean distance matrix analysis. Results:  Elongation of the coronoid process was identified in CEBPB(+/-) (P ≤ 0.046) and CEBPB(-/-) 12-month-olds (P ≤ 0.028) but not in 14-day-olds (P ≥ 0.217) and 0-day-olds (P ≥ 0.189) of either genotype. Formation of supernumerary teeth in CEBPB(-/-) adult mice was demonstrated (χ(2 ) =( ) 6.00, df = 1, P = 0.014). Conclusions:  CEBPB deficiency was related to elongation of the coronoid process and formation of supernumerary teeth. The mandibular and dental phenotypes of CEBPB deficiency were unseen by the 14th day after birth. Future investigations into the influence of CEBPB on mandibular and dental development are needed.

Katsu Takahashi - One of the best experts on this subject based on the ideXlab platform.

  • loss of stemness emt and supernumerary tooth formation in CEBPB runx2 murine incisors
    Scientific Reports, 2018
    Co-Authors: Kazuyuki Saito, Boyen Huang, Katsu Takahashi, Honoka Kiso, Yumiko Togo, Hiroko Tsukamoto, Masakazu Asahara, Sayaka Mishima, Masaki Nagata, Machiko Iida
    Abstract:

    Adult CEBPB KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, CEBPB acts upstream of Sox2 to regulate stemness. In this study, CEBPB KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a CEBPB knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell line presented a similar expression pattern. Therefore, the EMT enabled disengaged odontogenic epithelial stem cells to develop supernumerary teeth. CEBPB and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin expression, and Decorin-positive staining in the periapical region, indicating their involvement in supernumerary tooth formation. CEBPB and Runx2 acted synergistically and played an important role in the formation of supernumerary teeth in adult incisors.

  • Loss of Stemness, EMT, and Supernumerary Tooth Formation in CEBPB −/− Runx2 +/− Murine Incisors
    Nature Publishing Group, 2018
    Co-Authors: Kazuyuki Saito, Boyen Huang, Katsu Takahashi, Honoka Kiso, Yumiko Togo, Hiroko Tsukamoto, Masakazu Asahara, Sayaka Mishima, Masaki Nagata, Machiko Iida
    Abstract:

    Abstract Adult CEBPB KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, CEBPB acts upstream of Sox2 to regulate stemness. In this study, CEBPB KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a CEBPB knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell line presented a similar expression pattern. Therefore, the EMT enabled disengaged odontogenic epithelial stem cells to develop supernumerary teeth. CEBPB and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin expression, and Decorin-positive staining in the periapical region, indicating their involvement in supernumerary tooth formation. CEBPB and Runx2 acted synergistically and played an important role in the formation of supernumerary teeth in adult incisors

  • prospective signs of cleidocranial dysplasia in CEBPB deficiency
    Journal of Biomedical Science, 2014
    Co-Authors: Boyen Huang, Katsu Takahashi, Ernest A Jennings, Pongthorn Pumtangon, Honoka Kiso, Yumiko Togo, Kazuyuki Saito, Manabu Sugai, Shizuo Akira
    Abstract:

    Although runt-related transcription factor 2 (RUNX2) has been considered a determinant of cleidocranial dysplasia (CCD), some CCD patients were free of RUNX2 mutations. CCAAT/enhancer-binding protein beta (CEBPB) is a key factor of Runx2 expression and our previous study has reported two CCD signs including hyperdontia and elongated coronoid process of the mandible in CEBPB deficient mice. Following that, this work aimed to conduct a case-control study of thoracic, zygomatic and masticatory muscular morphology to propose an association between musculoskeletal phenotypes and deficiency of CEBPB, using a sample of CEBPB-/-, CEBPB+/- and CEBPB+/+ adult mice. Somatic skeletons and skulls of mice were inspected with soft x-rays and micro-computed tomography (μCT), respectively. Zygomatic inclination was assessed using methods of coordinate geometry and trigonometric function on anatomic landmarks identified with μCT. Masseter and temporal muscles were collected and weighed. Expression of CEBPB was examined with a reverse transcriptase polymerase chain reaction (RT-PCR) technique. CEBPB-/- mice displayed hypoplastic clavicles, a narrow thoracic cage, and a downward tilted zygomatic arch (p < 0.001). Although CEBPB+/- mice did not show the phenotypes above (p = 0.357), a larger mass percentage of temporal muscles over masseter muscles was seen in CEBPB+/- littermates (p = 0.012). The mRNA expression of CEBPB was detected in the clavicle, the zygoma, the temporal muscle and the masseter muscle, respectively. Prospective signs of CCD were identified in mice with CEBPB deficiency. These could provide an additional aetiological factor of CCD. Succeeding investigation into interactions among CEBPB, Runx2 and musculoskeletal development is indicated.

  • phenotypes of ccaat enhancer binding protein beta deficiency hyperdontia and elongated coronoid process
    Oral Diseases, 2013
    Co-Authors: Boyen Huang, Katsu Takahashi, Honoka Kiso, Yumiko Togo, Kazuyuki Saito, Manabu Sugai, Shizuo Akira, Tomoko Sakatagoto, Hiroko Tsukamoto, Akira Shimizu
    Abstract:

    Objectives:  This investigation aimed to conduct a case-control study of mandibular morphology and dental anomalies to propose a relationship between mandibular/dental phenotypes and deficiency of CCAAT/enhancer-binding protein beta (CEBPB). Materials and methods:  Skulls of CEBPB(-/-) , CEBPB(+/-) and CEBPB(+/+) mice were inspected with micro-computed tomography. Mandibular morphology was assessed with a method of Euclidean distance matrix analysis. Results:  Elongation of the coronoid process was identified in CEBPB(+/-) (P ≤ 0.046) and CEBPB(-/-) 12-month-olds (P ≤ 0.028) but not in 14-day-olds (P ≥ 0.217) and 0-day-olds (P ≥ 0.189) of either genotype. Formation of supernumerary teeth in CEBPB(-/-) adult mice was demonstrated (χ(2 ) =( ) 6.00, df = 1, P = 0.014). Conclusions:  CEBPB deficiency was related to elongation of the coronoid process and formation of supernumerary teeth. The mandibular and dental phenotypes of CEBPB deficiency were unseen by the 14th day after birth. Future investigations into the influence of CEBPB on mandibular and dental development are needed.