Guanine and nucleotide binding protein 3 promotes odonto/osteogenic differentiation of apical papilla stem cells via JNK and ERK signaling pathways

Zhang, Yang; Yuan, Lichan; Li, Meng; Fang, Mengru; Guo, Shuyu; Wang, Dongyue; Ma, Junqing; Wang, Lin

doi:10.3892/ijmm.2018.3984

Cited by 4 publications

(8 citation statements)

References 54 publications

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“…Notably, GNAI3 has been identified as one of these disease-related proteins after GATA4 deletion by isobaric tags for relative and absolute quantification (iTRAQ) method [27]. Accordingly, we inferred that Gnai3 was closely related to osteogenesis processes, and our previous research on the role of Gnai3 in odontogenesis and osteogenesis in stem cells from the apical papilla preliminary supported this hypothesis [8]. In this study, both in vitro and in vivo knockdown of Gnai3 were conducted, and the obtained results were in agreement with our hypothesis.…”

Section: Discussionsupporting

confidence: 51%

“…Importantly, GNAI3 has been found to hold a potential correlation with cartilage degeneration in the rat model of osteoarthritis [7]. However, the mechanistic connection of GNAI3 with osteogenesis remains poorly understood [8]. The homeobox genes distal less homeobox 5 (DLX5) and distal less homeobox 6 (DLX6) play critical functions in cranial neural crest cells (NCCs) and drive the primary normal lower jaw patterning.…”

Section: Introductionmentioning

confidence: 99%

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Mir24-2-5p suppresses the osteogenic differentiation with Gnai3 inhibition presenting a direct target via inactivating JNK-p38 MAPK signaling axis

Li¹,

Yuan²,

Ni³

et al. 2021

Int. J. Biol. Sci.

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Background: Congenital anomalies are increasingly becoming a global pediatric health concern, which requires immediate attention to its early diagnosis, preventive strategies, and efficient treatments. Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 (Gnai3) gene mutation has been demonstrated to cause congenital small jaw deformity, but the functions of Gnai3 in the disease-specific microRNA (miRNA) upregulations and their downstream signaling pathways during osteogenesis have not yet been reported. Our previous studies found that the expression of Mir24-2-5p was significantly downregulated in the serum of young people with overgrowing mandibular, and bioinformatics analysis suggested possible binding sites of Mir24-2-5p in the Gnai3 3'UTR region. Therefore, this study was designed to investigate the mechanism of Mir24-2-5p-mediated regulation of Gnai3 gene expression and explore the possibility of potential treatment strategies for bone defects. Methods: Synthetic miRNA mimics and inhibitors were transduced into osteoblast precursor cells to regulate Mir24-2-5p expression. Dual-luciferase reporter assay was utilized to identify the direct binding of Gnai3 and its regulator Mir24-2-5p. Gnai3 levels in osteoblast precursor cells were downregulated by shRNA (shGnai3). Agomir, Morpholino Oligo (MO), and mRNA were microinjected into zebrafish embryos to control mir24-2-5p and gnai3 expression. Relevant expression levels were determined by the qRT-PCR and Western blotting. CCK-8 assay, flow cytometry, and transwell migration assays were performed to assess cell proliferation, apoptosis, and migration. ALP, ARS and Von Kossa staining were performed to observe osteogenic differentiation. Alcian blue staining and calcein immersions were performed to evaluate the embryonic development and calcification of zebrafish. Results: The expression of Mir24-2-5p was reduced throughout the mineralization process of osteoblast precursor cells. miRNA inhibitors and mimics were transfected into osteoblast precursor cells. Cell proliferation, migration, osteogenic differentiation, and mineralization processes were measured, which showed a reverse correlation with the expression of Mir24-2-5p. Dual-luciferase reporter gene detection assay confirmed the direct interaction between Mir24-2-5p and Gnai3 mRNA. Moreover, in osteoblast precursor cells treated with Mir24-2-5p inhibitor, the expression of Gnai3 gene was increased, suggesting that Mir24-2-5p negatively targeted Gnai3. Silencing of Gnai3 inhibited osteoblast precursor cells proliferation, migration, osteogenic differentiation, and mineralization. Promoting effects of osteoblast precursor cells proliferation, migration, osteogenic differentiation, and mineralization by low expression of Mir24-2-5p was partially rescued upon silencing of Gnai3. In vivo, mir24-2-5p Agomir microinjection into zebrafish embryo resulted in shorter body length, smaller and retruded mandible, decreased cartilage development, and vertebral calcification, which was partially resc...

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Mir24-2-5p suppresses the osteogenic differentiation with Gnai3 inhibition presenting a direct target via inactivating JNK-p38 MAPK signaling axis

Li¹,

Yuan²,

Ni³

et al. 2021

Int. J. Biol. Sci.

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“…Mammalian TAS2Rs are expressed in several extra-gustatory tissues, e.g., the upper airways, , lungs, gastrointestinal tract, , brain, bladder, and testis, as well as immune competent cells, such as blood monocytes and leukocytes and gingival fibroblasts. , For gingival fibroblasts, Zhou et al recently published the protein expression of guanine nucleotide-binding protein G subunit alpha 3 (GNAT3), an upstream GPCR signaling protein, and provided results that suggest an involvement of TAS2Rs in cellular downstream inflammatory responses . In the here-presented work, the HGF-1 cells studied were stained positive for GNAI3, thereby confirming the presence of another signaling subunit in addition to GNAT3 reported by Zhou et al In recent works, it has been shown that in stem cells of the apical papilla (SCAPs), GNAI3 plays an important role in mineralization and tissue regeneration via the c-Jun N-terminal kinase (JNK) and the extracellular-signal regulated kinase (ERK) signaling . For HGF cells, presenting the predominant cell type in gingival connective tissue, GNAI3 is known to promote wound healing by promoting the generation of an extracellular matrix.…”

Section: Discussionmentioning

confidence: 81%

Human Gingival Fibroblasts as a Novel Cell Model Describing the Association between Bitter Taste Thresholds and Interleukin-6 Release

Tiroch

Dunkel

Sterneder

et al. 2023

J. Agric. Food Chem.

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Human gingival fibroblast cells (HGF-1 cells) present an important cell model to investigate the gingiva's response to inflammatory stimuli such as lipopolysaccharides from Porphyromonas gingivalis (Pg-LPS). Recently, we demonstrated transresveratrol to repress the Pg-LPS evoked release of the pro-inflammatory cytokine interleukin−6 (IL-6) via involvement of bitter taste sensing receptor TAS2R50 in HGF-1 cells. Since HGF-1 cells express most of the known 25 TAS2Rs, we hypothesized an association between a compound's bitter taste threshold and its repressing effect on the Pg-LPS evoked IL-6 release by HGF-1 cells. To verify our hypothesis, 11 compounds were selected from the chemical bitter space and subjected to the HGF-1 cell assay, spanning a concentration range between 0.1 μM and 50 mM. In the first set of experiments, the specific role of TAS2R50 was excluded by results from structurally diverse TAS2R agonists and antagonists and by means of a molecular docking approach. In the second set of experiments, the HGF-1 cell response was used to establish a linear association between a compound's effective concentration to repress the Pg-LPS evoked IL-6 release by 25% and its bitter taste threshold concentration published in the literature. The Pearson correlation coefficient revealed for this linear association was R 2 = 0.60 (p < 0.01), exceeding respective data for the test compounds from a well-established native cell model, the HGT-1 cells, with R 2 = 0.153 (p = 0.263). In conclusion, we provide a predictive model for bitter tasting compounds with a potential to act as anti-inflammatory substances.

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“…GNAI3 is primarily expressed in Hertwig's epithelial root sheath (HERS) and the surrounding mesenchyme in mice. Moreover, knockdown of GNAI3 could inhibit the proliferation, migration, and odonto/osteogenic differentiation of CD90 + /CD44 + /CD45 − /CD14 − SCAPs by inactivating c-Jun N-terminal kinase (JNK) and extracellular-signal regulated kinase (ERK) signaling pathways [ 117 ].…”

Section: Key Markers Of Dental-derived Mscsmentioning

confidence: 99%

Key Markers and Epigenetic Modifications of Dental-Derived Mesenchymal Stromal Cells

Chen

Zheng

Rao

et al. 2021

Stem Cells International

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As a novel research hotspot in tissue regeneration, dental-derived mesenchymal stromal cells (MSCs) are famous for their accessibility, multipotent differentiation ability, and high proliferation. However, cellular heterogeneity is a major obstacle to the clinical application of dental-derived MSCs. Here, we reviewed the heterogeneity of dental-derived MSCs firstly and then discussed the key markers and epigenetic modifications related to the proliferation, differentiation, immunomodulation, and aging of dental-derived MSCs. These messages help to control the composition and function of dental-derived MSCs and thus accelerate the translation of cell therapy into clinical practice.

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Guanine and nucleotide binding protein 3 promotes odonto/osteogenic differentiation of apical papilla stem cells via JNK and ERK signaling pathways

Cited by 4 publications

References 54 publications

Mir24-2-5p suppresses the osteogenic differentiation with Gnai3 inhibition presenting a direct target via inactivating JNK-p38 MAPK signaling axis

Mir24-2-5p suppresses the osteogenic differentiation with Gnai3 inhibition presenting a direct target via inactivating JNK-p38 MAPK signaling axis

Human Gingival Fibroblasts as a Novel Cell Model Describing the Association between Bitter Taste Thresholds and Interleukin-6 Release

Key Markers and Epigenetic Modifications of Dental-Derived Mesenchymal Stromal Cells

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