GREM1 通过与 YWHAH 的关联负性调控牙髓干细胞的骨质/牙本质分化

Shu Diao, Xiao Han, Wei Long Ye, Chen Zhang, Dong Mei Yang, Zhi Peng Fan, Song Lin Wang
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引用次数: 0

摘要

目的研究牙髓干细胞(DPSCs)中Gremlin1(GREM1)和酪氨酸3-单氧化酶/色氨酸5-单氧化酶活化蛋白eta(YWHAH)的生物调控功能,并确定其潜在的分子机制:方法:采用碱性磷酸酶(ALP)活性、茜素红染色、划痕迁移试验和裸鼠体内外骨/牙源性标志物检测来评估骨/牙源性分化。采用免疫共沉淀和多肽芯片检测相关分子机制:数据显示,敲除 GREM1 可促进 ALP 活性、体外矿化和成骨/成牙分化标记物的表达,并增强体内 DPSCs 的成骨/成牙作用。GREM1 与 DPSCs 中的 YWHAH 结合,并确定了结合位点。体外敲除YWHAH抑制了DPSCs的骨/牙质生成,而过表达YWHAH促进了DPSCs在体外和体内的骨/牙质生成:综上所述,研究结果凸显了GREM1-YWHAH在DPSCs骨/牙生成过程中的关键作用。
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GREM1 Negatively Regulates Osteo-/Dentinogenic Differentiation of Dental Pulp Stem Cells via Association with YWHAH.

Objective: To investigate the biological regulatory function of Gremlin1 (GREM1) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta (YWHAH) in dental pulp stem cells (DPSCs), and determine the underlying molecular mechanism involved.

Methods: Alkaline phosphatase (ALP) activity, alizarin red staining, scratch migration assays and in vitro and in vivo osteo-/dentinogenic marker detection of bone-like tissue generation in nude mice were used to assess osteo-/dentinogenic differentiation. Coimmunoprecipitation and polypeptide microarray assays were employed to detect the molecular mechanisms involved.

Results: The data revealed that knockdown of GREM1 promoted ALP activity, mineralisation in vitro and the expression of osteo-/dentinogenic differentiation markers and enhanced osteo-/ dentinogenesis of DPSCs in vivo. GREM1 bound to YWHAH in DPSCs, and the binding site was also identified. Knockdown of YWHAH suppressed the osteo-/dentinogenesis of DPSCs in vitro, and overexpression of YWHAH promoted the osteo-/dentinogenesis of DPSCs in vitro and in vivo.

Conclusion: Taken together, the findings highlight the critical roles of GREM1-YWHAH in the osteo-/dentinogenesis of DPSCs.

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Application of Chairside CAD/CAM and Its Influencing Factors among Chinese Dental Practitioners: a Crosssectional Study. CB1 Promotes Osteogenic Differentiation Potential of Periodontal Ligament Stem Cells by Enhancing Mitochondrial Transfer of Bone Marrow Mesenchymal Stem Cells. Establishment of an Animal Model of Oral Squamous Cell Carcinoma Invading the Mandible. GREM1 Negatively Regulates Osteo-/Dentinogenic Differentiation of Dental Pulp Stem Cells via Association with YWHAH. PHD2 shRNA-Modified Bone Marrow Mesenchymal Stem Cells Facilitate Periodontal Bone Repair in Response to Inflammatory Condition.
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