KDM1A regulated the osteo/dentinogenic differentiation process of the stem cells of the apical papilla via binding with PLOD2

Background Tissue regeneration mediated by mesenchymal stem cells (MSCs) is deemed a desirable way to repair teeth and craniomaxillofacial tissue defects. Nevertheless, the molecular mechanisms about cell proliferation and committed differentiation of MSCs remain obscure. Previous researches have proved that lysine demethylase 2A (KDM2A) performed significant function in the regulation of MSC proliferation and differentiation. SNRNP200, as a co-binding factor of KDM2A, its potential effect in regulating MSCs’ function is still unclear. Therefore, stem cells from the apical papilla (SCAPs) were used to investigate the function of SNRNP200 in this research. Methods The alkaline phosphatase (ALP) activity assay, Alizarin Red staining, and osteogenesis-related gene expressions were used to examine osteo−/dentinogenic differentiation potential. Carboxyfluorescein diacetate, succinimidyl ester (CFSE) and cell cycle analysis were applied to detect the cell proliferation. Western blot analysis was used to evaluate the expressions of cell cycle-related proteins. Results Depletion of SNRNP200 caused an obvious decrease of ALP activity, mineralization formation and the expressions of osteo−/dentinogenic genes including RUNX2, DSPP, DMP1 and BSP. Meanwhile, CFSE and cell cycle assays revealed that knock-down of SNRNP200 inhibited the cell proliferation and blocked cell cycle at the G2/M and S phase in SCAPs. In addition, it was found that depletion of SNRNP200 up-regulated p21 and p53, and down-regulated the CDK1, CyclinB, CyclinE and CDK2. Conclusions Depletion of SNRNP200 repressed osteo−/dentinogenic differentiation potentials and restrained cell proliferation through blocking cell cycle progression at the G2/M and S phase, further revealing that SNRNP200 has crucial effects on preserving the proliferation and differentiation potentials of dental tissue-derived MSCs.

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“…Then the gel was stained and cut for protein mass spectrometry analysis. The detailed procedures refer to our previous research [53].…”

Section: Protein Mass Spectrometrymentioning

confidence: 99%

Depletion of SNRNP200 inhibits the osteo−/dentinogenic differentiation and cell proliferation potential of stem cells from the apical papilla

Yang

Shi

et al. 2020

BMC Dev Biol

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“…It was reported that KDM1A in SCAP regulatory mechanisms of dynamic osteo/dentinogenic differentiation showed more diverse outcomes when applied in vitro than in vivo. However, in the final outcome of KDM1A inhibition, it promoted osteo/dentinogenesis in vivo [123]. Moreover, H2S proved to aid in the differentiation of DPSCs and dentin formation in vitro and in vivo via Ca 2+ homeostasis and Ca 2+ influx/GSK3β/(glycogen synthase kinase-3β) β-catenin cascade response.…”

Section: Signaling Moleculesmentioning

confidence: 99%

Tissue Engineering Approaches for Enamel, Dentin, and Pulp Regeneration: An Update

Ahmed

Abouauf

AbuBakr

et al. 2020

Stem Cells International

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Stem/progenitor cells are undifferentiated cells characterized by their exclusive ability for self-renewal and multilineage differentiation potential. In recent years, researchers and investigations explored the prospect of employing stem/progenitor cell therapy in regenerative medicine, especially stem/progenitor cells originating from the oral tissues. In this context, the regeneration of the lost dental tissues including enamel, dentin, and the dental pulp are pivotal targets for stem/progenitor cell therapy. The present review elaborates on the different sources of stem/progenitor cells and their potential clinical applications to regenerate enamel, dentin, and the dental pulpal tissues.

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“…The protein extraction and the gel electrophoresis tests were performed as previously described (Ge et al, 2014;Lv et al, 2016;Wang et al, 2018 2.5 | Alkaline phosphatase (ALP) activity assay and alizarin red detection SCAPs were cultured in mineralization-inducing medium (100 µM/ml ascorbic acid, 2 mM β-glycerophosphate, 1.8 mM KH 2 PO 4 and 10 nM dexamethasone). The ALP activity assay and Alizarin red detection were performed as previously described (Ge et al, 2014;Lv et al, 2016;Wang et al, 2018).…”

Section: The Western Blotmentioning

confidence: 99%

“…MSCs (Wang et al, 2018). Another study reported that KDM1A could also repress RUNX2 via H3K4me1 demethylation in myoblasts (Munehira, Yang, & Gozani, 2017).…”

Section: Kdm1a Inhibited the Migration And Chemotaxis Abilities Of mentioning

confidence: 99%

Homeobox C8 inhibited the osteo‐/dentinogenic differentiation and migration ability of stem cells of the apical papilla via activating KDM1A

Yang

Liang

Cao

et al. 2020

Journal Cellular Physiology

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Enhancing the functions of mesenchymal stem cells (MSCs) is considered a potential approach for promoting tissue regeneration. In the present study, we investigate the role of HOXC8 in regulating differentiation and migration by using stem cells of the apical papilla (SCAPs). Our results showed that overexpression of HOXC8 suppressed the osteo‐/dentinogenic differentiation, as detected by measuring alkaline phosphatase activity, in vitro mineralization, and the expressions of dentin sialophosphoprotein, dentin matrix acidic phosphoprotein 1, bone sialoprotein, runt‐related transcription factor 2, and osterix in SCAPs, and inhibited in vivo osteo‐/dentinogenesis of SCAPs. In addition, knockdown of HOXC8 promoted the osteo‐/dentinogenic differentiation potentials of SCAPs. Mechanically, HOXC8 enhanced KDM1A transcription by directly binding to its promoter. HOXC8 and KDM1A also inhibited the migration and chemotaxis abilities of SCAPs. To sum up, HOXC8 negatively regulated the osteo‐/dentinogenic differentiation and migration abilities of SCAPs by directly enhancing KDM1A transcription and indicated that HOXC8 and KDM1A could serve as potential targets for enhancing dental MSC mediated tissue regeneration.

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KDM1A regulated the osteo/dentinogenic differentiation process of the stem cells of the apical papilla via binding with PLOD2

Cited by 18 publications

References 34 publications

Depletion of SNRNP200 inhibits the osteo−/dentinogenic differentiation and cell proliferation potential of stem cells from the apical papilla

Depletion of SNRNP200 inhibits the osteo−/dentinogenic differentiation and cell proliferation potential of stem cells from the apical papilla

Tissue Engineering Approaches for Enamel, Dentin, and Pulp Regeneration: An Update

Homeobox C8 inhibited the osteo‐/dentinogenic differentiation and migration ability of stem cells of the apical papilla via activating KDM1A

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