The role of runt-related transcription factor 2 (Runx2) in the late stage of odontoblast differentiation and dentin formation

Li, Shiting; Kong, Han-Bae; Yao, Naihui; Yu, Qing; Wang, Ping; Lin, Yu‐Chi; Wang, Jing; Kuang, Rongze; Zhao, Xuyao; Xu, Jie; Zhu, Qinglin; Ni, Longxing

doi:10.1016/j.bbrc.2011.06.065

Cited by 81 publications

(54 citation statements)

References 18 publications

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“…The expression of osteogenesis or odontogenesis-related genes, such as Col1a1, Col1a2, osteopontin, BSP, OCN, fibronectin, MMP13, OPG, and DSPP, can be upregulated by Runx2 [22]–[24]. The effect of Runx2 during odontoblastic differentiation is dependent on the differentiation state of the target cells [21], [22]. In our study, we demonstrated that Runx2 was highly expressed in the odontoblast-like cells and pulp cells beneath the perforation in the process of reparative dentin formation.…”

Section: Discussionmentioning

confidence: 99%

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β-Catenin Enhances Odontoblastic Differentiation of Dental Pulp Cells through Activation of Runx2

Han

Zheng

et al. 2014

PLoS ONE

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An intense stimulus can cause death of odontoblasts and initiate odontoblastic differentiation of stem/progenitor cell populations of dental pulp cells (DPCs), which is followed by reparative dentin formation. However, the mechanism of odontoblastic differentiation during reparative dentin formation remains unclear. This study was to determine the role of β-catenin, a key player in tooth development, in reparative dentin formation, especially in odontoblastic differentiation. We found that β-catenin was expressed in odontoblast-like cells and DPCs beneath the perforation site during reparative dentin formation after direct pulp capping. The expression of β-catenin was also significantly upregulated during odontoblastic differentiation of in vitro cultured DPCs. The expression pattern of runt-related transcription factor 2 (Runx2) was similar to that of β-catenin. Immunofluorescence staining indicated that Runx2 was also expressed in β-catenin–positive odontoblast-like cells and DPCs during reparative dentin formation. Knockdown of β-catenin disrupted odontoblastic differentiation, which was accompanied by a reduction in β-catenin binding to the Runx2 promoter and diminished expression of Runx2. In contrast, lithium chloride (LiCl) induced accumulation of β-catenin produced the opposite effect to that caused by β-catenin knockdown. In conclusion, it was reported in this study for the first time that β-catenin can enhance the odontoblastic differentiation of DPCs through activation of Runx2, which might be the mechanism involved in odontoblastic differentiation during reparative dentin formation.

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Section: Discussionmentioning

confidence: 99%

“…Among those, Runx2 is a transcriptional factor and known master regulator in controlling osteoblast and odontoblast differentiation [21]. It has been shown that expression of genes that are required for osteoblastic or odontoblastic differentiation is regulated by Runx2 [22]–[24].…”

Section: Introductionmentioning

confidence: 99%

β-Catenin Enhances Odontoblastic Differentiation of Dental Pulp Cells through Activation of Runx2

Han

Zheng

et al. 2014

PLoS ONE

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“…RUNX2 peaked early at week 1, followed by ALP, which was activated first at day 12 and then at day 24. OPN, which is activated by RUNX2 [62], did not show activation until day 18, with the highest levels seen at day 24, showing continuous differentiation throughout the study. The expression of DMP1 was limited after 24 days, which does not agree with the study by Mikami et al which showed early expression of DMP1 from mRNA using RT-PCR when using dexamethasone as stimulant [63].…”

Section: Discussionmentioning

confidence: 99%

Influence of substrate curvature on osteoblast orientation and extracellular matrix deposition

et al. 2013

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BackgroundThe effects of microchannel diameter in hydroxyapatite (HAp) substrates on osteoblast behavior were investigated in this study. Microchannels of 100, 250 and 500 μm diameter were created on hydroxyapatite disks. The changes in osteoblast precursor growth, differentiation, extra cellular matrix (ECM) secretion and cell attachment/orientation were investigated as a function of microchannel diameter.ResultsCurvature did not impact cellular differentiation, however organized cellular orientation was achieved within the 100 and 250 μm microchannels (mc) after 6 days compared to the 12 days it took for the 500mc group, while the flat substrate remained disorganized. Moreover, the 100, 250 and 500mc groups expressed a specific shift in orientation of 17.45°, 9.05°, and 22.86° respectively in 24 days. The secreted/mineralized ECM showed the 100 and 250mc groups to have higher modulus (E) and hardness (h) (E = 42.6GPa; h = 1.6GPa) than human bone (E = 13.4-25.7GPa; h = 0.47-0.74GPa), which was significantly greater than the 500mc and control groups (p < 0.05). It was determined that substrate curvature affects the cell orientation, the time required for initial response, and the shift in orientation with time.ConclusionsThese findings demonstrate the ability of osteoblasts to organize and mineralize differentially in microchannels similar to those found in the osteons of compact bone. These investigations could lead to the development of osteon-like scaffolds to support the regeneration of organized bone.

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“…Alternatively, the absence of DSPP could affect the production of growth factors, which in turn might promote chondrogenic cell differentiation. For example, overexpression of Runx2 was reported to downregulate DSPP expression [41]. This suggests that there are direct or indirect interactions between DSPP and Runx2.…”

Section: Figmentioning

confidence: 99%

Dentin Sialophosphoprotein: A Regulatory Protein for Dental Pulp Stem Cell Identity and Fate

Guo

Lim

Dong

et al. 2014

Stem Cells and Development

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The dentin sialophosphoprotein (dspp) transcript is expressed during tooth development as a DSPP precursor protein, which then undergoes cleavage to form mature dentin sialoprotein (DSP) and phosphophoryn (PP) proteins. Previous studies using DSPP-knockout (KO) mice have reported that these animals have hypomineralized teeth, thin dentin, and a large dental pulp chamber, similar to those from patients with dentinogenesis imperfecta III. However, there is no information about factors that regulate dental pulp stem cell lineage fate, a critical early event in the odontoblast-dentin mineralization scheme. To reveal the role of DSPP in odontoblast lineage differentiation during tooth development, we systematically examined teeth from wild-type (wt) and DSPP-KO C57BL/6 mice between the ages of postnatal day 1 and 3 months. We found developmental abnormalities not previously reported, such as circular dentin formation within dental pulp cells and altered odontoblast differentiation in DSPP-KO mice, even as early as 1 day after birth. Surprisingly, we also identified chondrocytelike cells in the dental pulp from KO-mice teeth. Thus, these studies that compare wt and DSPP-KO mice suggest that the expression of DSPP precursor protein is required for normal odontoblast lineage differentiation and that the absence of DSPP allows dental pulp cells to differentiate into chondrocyte-like cells, which could negatively impact pulpal wound healing and tissue regeneration.

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The role of runt-related transcription factor 2 (Runx2) in the late stage of odontoblast differentiation and dentin formation

Cited by 81 publications

References 18 publications

β-Catenin Enhances Odontoblastic Differentiation of Dental Pulp Cells through Activation of Runx2

β-Catenin Enhances Odontoblastic Differentiation of Dental Pulp Cells through Activation of Runx2

Influence of substrate curvature on osteoblast orientation and extracellular matrix deposition

Dentin Sialophosphoprotein: A Regulatory Protein for Dental Pulp Stem Cell Identity and Fate

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