GATA Binding Protein 4 Regulates Tooth Root Dentin Development <i>via</i> FBP1

Zhang, Yuxin; Fang, Mengru; Yang, Zhiwen; Qin, Wenhao; Guo, Shuyu; Ma, Junqing; Chen, Wenjing

doi:10.7150/ijbs.36567

Cited by 10 publications

(6 citation statements)

References 35 publications

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“…However, little is known about its role in tooth development. GATA4 has been identified as a novel regulator of root development and is important for odontoblast polarity because it promotes the growth and differentiation of dental mesenchymal cells by regulating glucose metabolism ( Zhang et al, 2020 ). Further study is needed to determine whether ZFPM2 and its cofactor GATA4 interact with BCOR during odontogenesis.…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanism of hyperactive tooth root formation in oculo-facio-cardio-dental syndrome

Soe

Ogawa²,

Moriyama³

2022

Front. Physiol.

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Mutations in the B-cell lymphoma 6 (BCL6) interacting corepressor (BCOR) cause oculo-facio-cardio-dental (OFCD) syndrome, a rare X-linked dominant condition that includes dental radiculomegaly among other characteristics. BCOR regulates downstream genes via BCL6 as a transcriptional corepressor. However, the molecular mechanism underlying the occurrence of radiculomegaly is still unknown. Thus, this study was aimed at identifying BCOR-regulated genetic pathways in radiculomegaly. The microarray profile of affected tissues revealed that the gene-specific transcriptional factors group, wherein nucleus factor 1B, distal-less homeobox 5, and zinc finger protein multitype 2 (ZFPM2) were the most upregulated, was significantly expressed in periodontal ligament (PDL) cells of the diseased patient with a frameshift mutation (c.3668delC) in BCOR. Wild-type BCOR overexpression in human periodontal ligament fibroblasts cells significantly hampered cellular proliferation and ZFPM2 mRNA downregulation. Promoter binding assays showed that wild-type BCOR was recruited in the BCL6 binding of the ZFPM2 promoter region after immunoprecipitation, while mutant BCOR, which was the same genotype as of our patient, failed to recruit these promoter regions. Knockdown of ZFPM2 expression in mutant PDL cells significantly reduced cellular proliferation as well as mRNA expression of alkaline phosphatase, an important marker of odontoblasts and cementoblasts. Collectively, our findings suggest that BCOR mutation-induced ZFPM2 regulation via BCL6 possibly contributes to hyperactive root formation in OFCD syndrome. Clinical data from patients with rare genetic diseases may aid in furthering the understanding of the mechanism controlling the final root length.

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Section: Discussionmentioning

confidence: 99%

Molecular mechanism of hyperactive tooth root formation in oculo-facio-cardio-dental syndrome

Soe

Ogawa²,

Moriyama³

2022

Front. Physiol.

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“…Specially labeled and chemically modified miRNA agomiR is stable and can maintain activity in bone marrow environments for at least 2 weeks. Two injections were added every 3 d until mice at P21 45 . At the end of the experiment, bone samples were analyzed as above.…”

Section: Methodsmentioning

confidence: 99%

GATA4-driven miR-206-3p signatures control orofacial bone development by regulating osteogenic and osteoclastic activity

Guo¹,

Gu²,

Ma³

et al. 2021

Theranostics

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Growth disorders in the orofacial bone development process may lead to orofacial deformities. The balance between bone matrix formation by mesenchymal lineage osteoblasts and bone resorption by osteoclasts is vital for orofacial bone development. Although the mechanisms of orofacial mesenchymal stem cells (OMSCs) in orofacial bone development have been studied intensively, the communication between OMSCs and osteoclasts remains largely unclear. Methods: We used a neural crest cell-specific knockout mouse model to investigate orofacial bone development in GATA-binding protein 4 (GATA4) morphants. We investigated the underlying mechanisms of OMSCs-derived exosomes (OMExos) on osteoclastogenesis and bone resorption activity in vitro . miRNAs were extracted from OMExos, and differences in miRNA abundances were determined using an Affymetrix miRNA array. Luciferase reporter assays were used to validate the binding between GATA4 and miR-206-3p in OMSCs and to confirm the putative binding of miR-206-3p and its target genes in OMSCs and osteoclasts. The regulatory mechanism of the GATA4-miR-206-3p axis in OMSC osteogenic differentiation and osteoclastogenesis was examined in vitro and in vivo . Results: Wnt1-Cre;Gata4 fl/fl mice (cKO) not only presented inhibited bone formation but also showed active bone resorption. Osteoclasts cocultured in vitro with cKO OMSCs presented an increased capacity for osteoclastogenesis, which was exosome-dependent. Affymetrix miRNA array analysis showed that miR-206-3p was downregulated in exosomes from shGATA4 OMSCs. Moreover, the transcriptional activity of miR-206-3p was directly regulated by GATA4 in OMSCs. We further demonstrated that miR-206-3p played a key role in the regulation of orofacial bone development by directly targeting bone morphogenetic protein-3 (Bmp3) and nuclear factor of activated T -cells, cytoplasmic 1 (NFATc1). OMExos and agomiR-206-3p enhanced bone mass in Wnt1-cre;Gata4 fl/fl mice by augmenting trabecular bone structure and decreasing osteoclast numbers. Conclusion: Our findings confirm that miR-206-3p is an important downstream factor of GATA4 that regulates the functions of OMSCs and osteoclasts. These results demonstrate the efficiency of OMExos and microRNA agomirs in promoting bone regeneration, which provide an ideal therapeutic tool for orofacial bone deformities in the future.

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“…Root development occurs after crown formation, which is initiated by the Hertwigs' epithelial root sheath 4,5 . Mesenchymal stem cells in tooth germ receive root development signals from the Hertwigs' epithelial root sheath.…”

Section: Introductionmentioning

confidence: 99%

SLIT3: a Novel Regulator of Odontogenic Differentiation through Akt/Wnt/β-catenin Signaling Pathway

Sun,

Jiang,

Liu

et al. 2024

Preprint

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The odontogenic differentiation of Stem cells from apical papilla (SCAP) is regulated by many extracellular matrix proteins, which plays a crucial role in dentin formation and regeneration. Extracellular matrix protein SLIT3, a classical axon guidance molecule, can link bone resorption to formation as clastokine. However, there is little information about SLIT3 in odontogenesis. Therefore, our study is aimed to explore the effects and possible mechanism of SLIT3 on the proliferation and differentiation of SCAP. Through Immunohistochemical staining and re-analysis of single-cell RNA sequencing and microarray datasets, we found that SLIT3 was expressed in the dental papilla and odontoblast layer of the developing molar tooth of mice. Real time polymerase chain reaction (RT-PCR) and Western blot assays also revealed an increased expression of SLIT3 during the odontogenic differentiation of SCAP. Afterwards, SLIT3 siRNA was used to knockdown SLIT3 and recombinant human SLIT3 (rhSLIT3) protein was used to treat SCAP. Cell Counting Kit-8 assays (CCK8) assays showed SLIT3 promoted proliferation of SCAP. Alkaline phosphatase (ALP) staining and Alizarin red staining were decreased/increased accordingly. Odontogenic markers DMP-1 and DSPP were also down-regulated/up-regulated. In addition, p-Akt and p-GSK3β levels were increased in rhSLIT3-treated SCAP and the movement into cell nucleus of β-catenin was promoted. The effect of SLIT3 was canceled after treatment with the inhibitor of Akt/Wnt/β-catenin signaling pathway. Taken together, our data show that SLIT3 could promote the proliferation and odontogenic differentiation of SCAP by activating Akt/Wnt/β-catenin signaling pathway.

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GATA Binding Protein 4 Regulates Tooth Root Dentin Development via FBP1

Cited by 10 publications

References 35 publications

Molecular mechanism of hyperactive tooth root formation in oculo-facio-cardio-dental syndrome

Molecular mechanism of hyperactive tooth root formation in oculo-facio-cardio-dental syndrome

GATA4-driven miR-206-3p signatures control orofacial bone development by regulating osteogenic and osteoclastic activity

SLIT3: a Novel Regulator of Odontogenic Differentiation through Akt/Wnt/β-catenin Signaling Pathway

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