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

Abstract

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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“…In terms of osteogenesis, it has been previously reported that SNRNP200 knockdown can inhibit the osteogenic/odontogenic differentiation of SCAPs (Su et al, 2020). In this study, we found that knockdown of SNRNP200 inhibited the ALP activity and mineralization ability in DPSCs, indicating that SNRNP200 might promote the odontogenic differentiation of DPSCs.…”

miR-6807-5p Inhibited the Odontogenic Differentiation of Human Dental Pulp Stem Cells Through Directly Targeting METTL7A

“…In addition, SNRNP200 is also involved in the process of mammalian cell cycle ( Ehsani et al, 2013 ). In terms of osteogenesis, it has been previously reported that SNRNP200 knockdown can inhibit the osteogenic/odontogenic differentiation of SCAPs ( Su et al, 2020 ). In this study, we found that knockdown of SNRNP200 inhibited the ALP activity and mineralization ability in DPSCs, indicating that SNRNP200 might promote the odontogenic differentiation of DPSCs.…”

Epigenetic control of mesenchymal stem cells orchestrates bone regeneration

“…MSCs proliferation can also be consistently inhibited by the knockdown of SNRNP200, a co-binding factor of KDM2A, by blocking MSCs in the G2/M and S phases of the cell cycle. Deleting SNRNP200 upregulated CDKN1A and p53 but downregulated CDK1, CYCB, CYCE, and CDK2 ( 153 ). Pharmacological G9a inhibition significantly enhanced MSCs proliferation ( 154 ).…”