Loss of Stat3 in Osterix+ cells impairs dental hard tissues development

Chan, Laiting; Lu, Jiarui; Feng, Xin; Lin, Lichieh; Yao, Yichen; Zhang, Xiaolei

doi:10.1186/s13578-023-01027-1

Cited by 3 publications

(1 citation statement)

References 45 publications

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“…Osterix (Osx/Sp7) is a specific transcription factor committed to the dentin-forming odontoblastic lineage. 21 The expression levels of Tomato + cells from Osx-cre; R26R tdTomato mice verified that OSX was highly expressed during odontoblast differentiation of dental MSCs, both M1 and M3 (Fig. S3a ).…”

Section: Resultsmentioning

confidence: 61%

PRX1-positive mesenchymal stem cells drive molar morphogenesis

Xu,

Gong,

Zhang

et al. 2024

Int J Oral Sci

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Mammalian teeth, developing inseparable from epithelial-mesenchymal interaction, come in many shapes and the key factors governing tooth morphology deserve to be answered. By merging single-cell RNA sequencing analysis with lineage tracing models, we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1+ cells within M1. These PRX1+ cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation. Deeper into the mechanisms, we have discovered that Wnt5a, bestowed by mesenchymal PRX1+ cells, stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway. The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1. Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs. These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.

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Section: Resultsmentioning

confidence: 61%

PRX1-positive mesenchymal stem cells drive molar morphogenesis

Xu,

Gong,

Zhang

et al. 2024

Int J Oral Sci

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Mijiao formula regulates NAT10-mediated Runx2 mRNA ac4C modification to promote bone marrow mesenchymal stem cell osteogenic differentiation and improve osteoporosis in ovariectomized rats

Xiao,

Huang,

Tang

et al. 2024

Journal of Ethnopharmacology

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Glutamine-αKG axis affects dentin regeneration and regulates osteo/odontogenic differentiation of mesenchymal adult stem cells via IGF2 m6A modification

Tian,

Gao,

et al. 2024

Preprint

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Background Multi-lineage differentiation of mesenchymal adult stem cells (m-ASCs) is crucial for tissue regeneration and accompanied with metabolism reprogramming, among which dental-pulp-derived m-ASCs has obvious advantage of easy accessibility. Stem cell fate determination and differentiation are closely related to metabolism status in cell microenvironment, which could actively interact with epigenetic modification. In recent years, glutamine-α-ketoglutarate(αKG) axis was proved to be related to aging, tumorigenesis, osteogenesis etc., while its role in m-ASCs still lack adequate research evidence. Methods We employed metabolomic analysis to explore the change pattern of metabolites during dental-pulp-derived m-ASCs differentiation. A murine incisor clipping model was established to investigate the influence of αKG on dental tissue repairment. shRNA technique was used to knockdown the expression of related key enzyme-dehydrogenase 1(GLUD1). RNA-seq, m6A evaluation and MeRIP-qPCR were used to dig into the underlying epigenetic mechanism. Results Here we found that the glutamine-αKG axis displayed an increased tendency along with the osteo/odontogenic differentiation of dental-pulp-derived m-ASCs, same as expression pattern of GLUD1. Further, the key metabolite αKG was found able to accelerate the repairment of clipped mice incisor and promote dentin formation. Exogenous DM-αKG was proved able to promote osteo/odontogenic differentiation of dental-pulp-derived m-ASCs, while the inhibition of glutamine-derived αKG level via GLUD1 knockdown had the opposite effect. Under the circumstance of GLUD1 knockdown, extracellular matrix(ECM)function and PI3k-Akt signaling pathway was screened out to be widely involved in the process with insulin-like growth factor 2 (IGF2) participation via RNA-seq. Inhibition of glutamine-αKG axis may affect IGF2 translation efficiency via m6A methylation and can be significantly rescued by αKG supplementation. Conclusion Our findings indicate that glutamine-αKG axis may epigenetically promote osteo/odontogenic differentiation of dental-pulp-derived m-ASCs and dentin regeneration, which provide a new research vision of potential dental tissue repairment therapy method or metabolite-based drug research.

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Loss of Stat3 in Osterix+ cells impairs dental hard tissues development

Cited by 3 publications

References 45 publications

PRX1-positive mesenchymal stem cells drive molar morphogenesis

PRX1-positive mesenchymal stem cells drive molar morphogenesis

Mijiao formula regulates NAT10-mediated Runx2 mRNA ac4C modification to promote bone marrow mesenchymal stem cell osteogenic differentiation and improve osteoporosis in ovariectomized rats

Glutamine-αKG axis affects dentin regeneration and regulates osteo/odontogenic differentiation of mesenchymal adult stem cells via IGF2 m6A modification

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