Regulation of miR-1-Mediated Connexin 43 Expression and Cell Proliferation in Dental Epithelial Cells
Many genes encoding growth factors, receptors, and transcription factors are induced by the epithelial-mesenchymal interaction during tooth development. Recently, numerous functions of microRNAs (miRNAs) are reportedly involved in organogenesis and disease. miRNAs regulate gene expression by inhibit...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.00156/full |
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| author | Tomoaki Nakamura Tsutomu Iwamoto Hannah M. Nakamura Yuki Shindo Kan Saito Aya Yamada Yoshihiko Yamada Satoshi Fukumoto Takashi Nakamura |
| author_facet | Tomoaki Nakamura Tsutomu Iwamoto Hannah M. Nakamura Yuki Shindo Kan Saito Aya Yamada Yoshihiko Yamada Satoshi Fukumoto Takashi Nakamura |
| author_sort | Tomoaki Nakamura |
| collection | DOAJ |
| description | Many genes encoding growth factors, receptors, and transcription factors are induced by the epithelial-mesenchymal interaction during tooth development. Recently, numerous functions of microRNAs (miRNAs) are reportedly involved in organogenesis and disease. miRNAs regulate gene expression by inhibiting translation and destabilizing mRNAs. However, the expression and function of miRNAs in tooth development remain poorly understood. This study aimed to analyze the expression of miRNAs produced during tooth development using a microarray system to clarify the role of miRNAs in dental development. miR-1 showed a unique expression pattern in the developing tooth. miR-1 expression in the tooth germ peaked on embryonic day 16.5, decreasing gradually on postnatal days 1 and 3. An in situ hybridization assay revealed that miR-1 is expressed at the cervical loop of the dental epithelium. The expression of miR-1 and connexin (Cx) 43, a target of miR-1, were inversely correlated both in vitro and in vivo. Knockdown of miR-1 induced the expression of Cx43 in dental epithelial cells. Interestingly, cells with miR-1 downregulation proliferated slower than the control cells. Immunocytochemistry revealed that Cx43 in cells with miR-1 knockdown formed both cell-cell gap junctions and hemichannels at the plasma membrane. Furthermore, the rate of ATP release was higher in cells with miR-1 knockdown than in control cells. Furthermore, Cx43 downregulation in developing molars was observed in Epiprofin-knockout mice, along with the induction of miR-1 expression. These results suggest that the expression pattern of Cx43 is modulated by miR-1 to control cell proliferation activity during dental epithelial cell differentiation. |
| first_indexed | 2024-12-21T10:58:55Z |
| format | Article |
| id | doaj.art-14851fb84ed641ab84f2e1b7363b34af |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T10:58:55Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-14851fb84ed641ab84f2e1b7363b34af2022-12-21T19:06:24ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-03-01810.3389/fcell.2020.00156513640Regulation of miR-1-Mediated Connexin 43 Expression and Cell Proliferation in Dental Epithelial CellsTomoaki Nakamura0Tsutomu Iwamoto1Hannah M. Nakamura2Yuki Shindo3Kan Saito4Aya Yamada5Yoshihiko Yamada6Satoshi Fukumoto7Takashi Nakamura8Division of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, JapanDepartment of Pediatric Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, JapanDivision of Nephrology and Endocrinology, Tohoku Medical and Pharmaceutical University, Sendai, JapanDivision of Molecular Pharmacology and Cell Biophysics, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai, JapanDivision of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, JapanDivision of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, JapanLaboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, United StatesDivision of Pediatric Dentistry, Department of Oral Health and Development Sciences, Tohoku University Graduate School of Dentistry, Sendai, JapanDivision of Molecular Pharmacology and Cell Biophysics, Department of Oral Biology, Tohoku University Graduate School of Dentistry, Sendai, JapanMany genes encoding growth factors, receptors, and transcription factors are induced by the epithelial-mesenchymal interaction during tooth development. Recently, numerous functions of microRNAs (miRNAs) are reportedly involved in organogenesis and disease. miRNAs regulate gene expression by inhibiting translation and destabilizing mRNAs. However, the expression and function of miRNAs in tooth development remain poorly understood. This study aimed to analyze the expression of miRNAs produced during tooth development using a microarray system to clarify the role of miRNAs in dental development. miR-1 showed a unique expression pattern in the developing tooth. miR-1 expression in the tooth germ peaked on embryonic day 16.5, decreasing gradually on postnatal days 1 and 3. An in situ hybridization assay revealed that miR-1 is expressed at the cervical loop of the dental epithelium. The expression of miR-1 and connexin (Cx) 43, a target of miR-1, were inversely correlated both in vitro and in vivo. Knockdown of miR-1 induced the expression of Cx43 in dental epithelial cells. Interestingly, cells with miR-1 downregulation proliferated slower than the control cells. Immunocytochemistry revealed that Cx43 in cells with miR-1 knockdown formed both cell-cell gap junctions and hemichannels at the plasma membrane. Furthermore, the rate of ATP release was higher in cells with miR-1 knockdown than in control cells. Furthermore, Cx43 downregulation in developing molars was observed in Epiprofin-knockout mice, along with the induction of miR-1 expression. These results suggest that the expression pattern of Cx43 is modulated by miR-1 to control cell proliferation activity during dental epithelial cell differentiation.https://www.frontiersin.org/article/10.3389/fcell.2020.00156/fulldental developmentdifferentiationmicroRNAcell proliferationconnexin 43 |
| spellingShingle | Tomoaki Nakamura Tsutomu Iwamoto Hannah M. Nakamura Yuki Shindo Kan Saito Aya Yamada Yoshihiko Yamada Satoshi Fukumoto Takashi Nakamura Regulation of miR-1-Mediated Connexin 43 Expression and Cell Proliferation in Dental Epithelial Cells Frontiers in Cell and Developmental Biology dental development differentiation microRNA cell proliferation connexin 43 |
| title | Regulation of miR-1-Mediated Connexin 43 Expression and Cell Proliferation in Dental Epithelial Cells |
| title_full | Regulation of miR-1-Mediated Connexin 43 Expression and Cell Proliferation in Dental Epithelial Cells |
| title_fullStr | Regulation of miR-1-Mediated Connexin 43 Expression and Cell Proliferation in Dental Epithelial Cells |
| title_full_unstemmed | Regulation of miR-1-Mediated Connexin 43 Expression and Cell Proliferation in Dental Epithelial Cells |
| title_short | Regulation of miR-1-Mediated Connexin 43 Expression and Cell Proliferation in Dental Epithelial Cells |
| title_sort | regulation of mir 1 mediated connexin 43 expression and cell proliferation in dental epithelial cells |
| topic | dental development differentiation microRNA cell proliferation connexin 43 |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.00156/full |
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