IGFBP5 enhances the dentinogenesis potential of dental pulp stem cells via JNK and ErK signalling pathways

Hao, Junling; Yang, Haoqing; Cao, Yangyang; Zhang, Chen

doi:10.1111/joor.13047

Cited by 20 publications

(16 citation statements)

References 34 publications

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“…Clusters 2 and 3 were minimal in Y1, but dominant in the other three samples, highly expressing IGFBP5, EFNB2, and POSTN (Figures 3B-D). These genes have been shown to be related to angiogenesis or odontogenesis of dental pulp (Du and Li, 2019;Hao et al, 2020;Yuan et al, 2019). They may play a role in the late growth of the human dental pulp.…”

Section: Subpopulation Characteristics Of Fibroblasts At Multiple Spa...mentioning

confidence: 99%

An atlas of human dental pulp cells in multiple spatial and temporal levels based on single-cell sequencing analysis

Ren

Wen

Zhao

et al. 2022

Preprint

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Background The dental pulp plays a crucial role in the long-term maintenance of teeth function. The progress of endodontic treatment and pulp tissue regeneration engineering has therapeutic potential. But regulation mechanisms of tooth development or regeneration dependent on dental stem cells were still not fully understood. So, it is urgently needed bridge the gaps between basic and clinical research. With single cell sequencing technology being applied in medical research, landscapes of human dental pulp cells had been initially outlined. However, the specific cellular heterogeneity of dental pulp cells, especially dental stem cells in different spatial and temporal levels are remain unclear. Methods Gene expression profiles of human dental pulp cells from four teeth with different developmental periods analyzed by 10x Genomics single-cell RNA sequencing were studied and cluster analysis. Multiple spatial and temporal characteristics of subpopulation of cells were further studied by signal pathway analysis, trajectory analysis stemness analysis. Results In this study, transcriptomic expression-based clustering analysis showed that dental pulp cells at different developmental points exist differences in number, not cell types. Pathway analysis revealed that early in development, the pulp may perform more developmentally relevant functions such as synthetic translation, while later it begins to differentiate into specific directions or retains functional characteristics for homeostasis maintenance. The importance of the stem cell microenvironment in human tooth development was evident. Subpopulations in early development stage were clearly identified in fibroblasts, odontoblasts and mesenchymal stem cells. Particularly, differentially expressed gene analysis and stemness analysis defined three subpopulations of dental pulp stem cells with greater stemness and potential for multiple differentiation. Combining the expression characteristics of the three cell subpopulations, some genes such as MIA, DGKI and so on that may contribute to the developmental differentiation of dental pulp stem cells were also uncovered Conclusion For the first time, the specific cellular heterogeneity of dental pulp cells, especially dental stem cells in different spatial and temporal level was proviede. Gene expression profile of early developing cells may help in cell screening for regenerative engineering and improve the success of dental pulp regeneration.

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Section: Subpopulation Characteristics Of Fibroblasts At Multiple Spa...mentioning

confidence: 99%

An atlas of human dental pulp cells in multiple spatial and temporal levels based on single-cell sequencing analysis

Ren

Wen

Zhao

et al. 2022

Preprint

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show abstract

“…Clusters 2 and 3 were minimal in Y1, but dominant in the other three samples, highly expressing IGFBP5 , EFNB2 , and POSTN ( Figures 3B–D ). These genes have been shown to be related to angiogenesis or odontogenesis of dental pulp ( Du and Li, 2019 ; Hao et al, 2020 ; Yuan et al, 2019 ). They may play a role in the late growth of the human dental pulp.…”

Section: Resultsmentioning

confidence: 99%

Atlas of human dental pulp cells at multiple spatial and temporal levels based on single-cell sequencing analysis

Ren¹,

Wen

Zhao³

et al. 2022

Front. Physiol.

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The dental pulp plays a crucial role in the long-term maintenance of tooth function. The progress of endodontic treatment and pulp tissue regeneration engineering has made pulp-regeneration therapy promising in clinical practice. However, the mechanisms of pulp regeneration and the role of dental stem cells in development and regeneration have not been fully elucidated. Bridging the gaps between clinical operation and basic research is urgently needed. With the application of single-cell sequencing technology in dental research, the landscapes of human dental pulp cells have begun being outlined. However, the specific cellular heterogeneity of dental pulp cells, especially that of dental stem cells, at different spatial and temporal levels, is still unclear. In this study, we used single-cell RNA sequencing analysis of pulp samples at four different developmental stages and combined the findings with immunohistochemical staining to explore the development of dental pulp and stem cells. The results revealed temporal changes in the proportion of pulp cells during development. For example, mononuclear phagocytes accounted for a higher proportion in early samples. Odontoblasts identified by DMP1 had a higher expression of ion channel-related and neurodevelopment-related genes. Subpopulations were identified in fibroblasts, odontoblasts, and mesenchymal stem cells. We identified a subclass of odontoblasts that expresses DGKI and RRBP1 present in early developmental samples. A population of earlier mesenchymal stem cells expressed the SEPTIN gene, which may have greater proliferative and differentiation potential. Furthermore, dental pulp stem cells can differentiate into two directions: mineralization and myogenesis. In summary, the specific cellular heterogeneity of dental pulp cells was revealed at different spatial and temporal levels. These findings may shed light on the mechanism of tooth development. The gene expression profile of developing pulp cells may help to select cells for regenerative engineering and improve the success of dental pulp regeneration.

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“…FP207) according to the manufacturer's protocols under the following conditions: 15 min of denaturation at 42˚C and 1 cycle of 1 min of denaturation at 95˚C and 40 cycles each of 5 sec of denaturation at 95˚C and 15 sec of amplification at 60˚C. The following primer sequences were used as previously described: human actin ( 22 ) forward, 5'-CATGTACGTTGCTATCCAGGC-3' and reverse, 5'-CTCCTTAATGTCACGCACGAT-3'; human ALP ( 22 ) forward, 5'-CCTCCTCGGAAGACACTCTG-3' and reverse, 5'-GCAGTGAAGGGCTTCTTGTC-3'; human RUNX2( 22 ) forward, 5'-CCACTGAACCAAAAAGAAATCCC-3' and reverse, 5'-GAAAACAACACATAGCCAAACGC-3'; human OCN ( 23 ) forward, 5'-GCGCTACCTGTATCAATGGC-3' and reverse, 5'-AACTCTCACAGTCCGGATT-3'; human dentin sialophosphoprotein (DSPP) ( 7 ) forward, 5'-CGACATAGGTCACAATGAGGATGTCG-3' and reverse, 5'-TTGCTTCCAGCTACTTGAGGTC-3'; human BSP ( 7 ) forward, 5'-CAGGCCACGATATTATCTTTACA-3'and reverse, 5'-CTCCTCTTCTTCCTCCTCCTC-3' and human OSX ( 24 ) forward, 5'-CTGTGAAACCTCAAGTCCTATGGA-3' and reverse, 5'-GCTCTGCAGTCAAGGGAGATG-3'. The relative gene expression was calculated according to the comparative 2 -ΔΔCq method and normalized to that of actin ( 25 ).…”

Section: Methodsmentioning

confidence: 99%

“…During pulp regeneration, the microenvironment can regulate the directional differentiation of stem cells, which in turn affects downstream processes, including the generation of new blood vessels, neurons and dentin, in the regenerated pulp-like tissues ( 6 ). In the majority of studies that previously investigated dental pulp-like tissue regeneration, the regulation of transplanted human dental pulp stem cell (hDPSC) differentiation serves an important role ( 7 , 8 ). Regulation of the stem cell microenvironment and its influence of the direct differentiation of stem cells has been a subject of intense research.…”

Section: Introductionmentioning

confidence: 99%

Salidroside promotes the osteogenic and odontogenic differentiation of human dental pulp stem cells through the BMP signaling pathway

Wei

Liu

et al. 2021

Exp Ther Med

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Regenerative endodontics, as an alternative approach, aims to regenerate dental pulp-like tissues and is garnering the attention of clinical dentists. This is due to its reported biological benefits for dental therapeutics. Stem cells and their microenvironment serve an important role in the process of pulp regeneration. Regulation of the stem cell microenvironment and the directed differentiation of stem cells is becoming a topic of intensive research. Salidroside (SAL) is extracted from the root of Rhodiola rosea and it has been reported that SAL exerts antiaging, neuroprotective, hepatoprotective, cardioprotective and anticancer effects. However, the ability of SAL to regulate the osteo/odontogenic differentiation of hDPSCs remains to be elucidated. In the present study, the effect of SAL on the proliferation and osteogenic/odontogenic differentiation of human dental pulp stem cells (hDPSCs) was investigated. This was achieved by performing CCK-8 ARS staining assay, reverse transcription-quantitative PCR to detect mRNA of ALP, OSX, RUNX2, OCN, DSPP and BSP, western blotting to detect the protein of MAPK, Smad1/5/8, OSX, RUNX2, BSP and GAPDH and immunofluorescence assays to detect DSPP. The results indicated that SAL promoted the cell viability and the osteogenic/odontogenic differentiation of hDPSCs whilst increasing the expression of genes associated with osteogenic/odontogenic differentiation by ARS staining assay. In addition, SAL promoted osteogenic and odontogenic differentiation by activating the phosphorylation of Smad1/5/8. Collectively, these findings suggest that SAL promoted the osteogenic and odontogenic differentiation of hDPSCs activating the BMP signaling pathway.

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IGFBP5 enhances the dentinogenesis potential of dental pulp stem cells via JNK and ErK signalling pathways

Cited by 20 publications

References 34 publications

An atlas of human dental pulp cells in multiple spatial and temporal levels based on single-cell sequencing analysis

An atlas of human dental pulp cells in multiple spatial and temporal levels based on single-cell sequencing analysis

Atlas of human dental pulp cells at multiple spatial and temporal levels based on single-cell sequencing analysis

Salidroside promotes the osteogenic and odontogenic differentiation of human dental pulp stem cells through the BMP signaling pathway

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