Runx2 modified dental pulp stem cells (DPSCs) enhance new bone formation during rapid distraction osteogenesis (DO)

Abstract Background: Many studies have found that circRNA plays a part in osteoblast differentiation. However, its mechanism remains unknown. Methods: High-throughput sequencing was used to identifield the different expression of circRNA during osteogenic dental pulp stem cells (DPSCs) differentiation. Luciferase report analysis and RT-qPCR were used to clarify the expression and regulation relationship among circ-FURIN, miR-125 and SOX11. The heterotopic bone formation experiment was further used to confirm the osteoblast differentiation of DPSC with different expression of circ-FURIN, miR-125 and SOX11. Results: Study indicated that circ-FURIN expression remarkably increased during osteoblast differentiation, yet circ-FURIN knockdown suppressed it. Bioinformatics and luciferase results discovered that miR-125 is the downstream target of circ-FURIN. Furthermore, circ-FURIN upregulation decreased miR-125 expression. MiR-125 upregulation restored the promotion effect of circ-FURIN on osteogenic DPSC differentiation. Luciferase report analysis verified that SOX11 is miR-125 downstream target. miR-125 overexpression suppressed osteogenic DPSC differentiation through targeting SOX11. SOX11 overexpression restored miR-125 inhibitory effect on osteogenic DPSC differentiation. In vivo experiments with heterotopic bone model suggested that circ-FURIN overexpression has crucial function to enhance heterotopic bone formation. Conclusions: In summary, circ-FURIN enhances osteoblast DPSC differentiation via the SOX11 signaling pathway by sponging miR-125. These findings suggest a novel therapeutic target for osteoporosis treatment.

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Human Dental Pulp Stem Cells in Rat Mandibular Bone Defects

Cells Tissues Organs ◽

10.1159/000502513 ◽

2019 ◽

Vol 207 (3-4) ◽

pp. 138-148 ◽

Cited By ~ 2

Author(s):

Rubia Teodoro Stuepp ◽

Priscilla Barros Delben ◽

Filipe Modolo ◽

Andrea Gonçalves Trentin ◽

Ricardo Castilho Garcez ◽

...

Keyword(s):

Stem Cells ◽

Bone Formation ◽

Dental Pulp ◽

Bone Defects ◽

Treated Group ◽

Dental Pulp Stem Cells ◽

Control Group ◽

Mandibular Bone ◽

Significant Difference ◽

Human Dental Pulp

This study aimed to evaluate the use of human dental pulp stem cells (hDPSCs) in non-critical-sized mandibular bone defects in rats. hDPSCs from permanent teeth were isolated and engrafted in mandibular bone defects in rats for 7, 14, and 28 days; bone defects without cells formed the control group. Samples were evaluated by scanning electron microscopy (SEM), light microscopy (hematoxylin and eosin staining), and the regeneration area was measured by the Image J program. Before surgery procedures, the human dental pulp cells were characterized as dental pulp stem cells: fusiform morphology, plastic-adherent; expression of CD105, CD73, and CD90; lack of expression of CD45 and CD34, and differentiated into osteoblasts, adipocytes, and chondroblasts. The results indicated that within 7 days the control group presented a pronounced bone formation when compared with the treated group (p < 0.05). After 14 days, the treated group showed an increase in bone formation, but with no statistical difference among the groups (p > 0.05). In the final evaluated period there was no difference between the control group and the treated group (p > 0.05). There was a significant difference between 7 and 14 days (p < 0.05) and between 7 and 28 days (p < 0.05) in the treated group. In conclusion, there is no evidence that the use of hDPSCs in the conditions of this study could improve bone formation in non-critical-sized mandibular bone defects.

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Efficacy of extracellular vesicles from dental pulp stem cells for bone regeneration in rat calvarial bone defects

Inflammation and Regeneration ◽

10.1186/s41232-021-00163-w ◽

2021 ◽

Vol 41 (1) ◽

Author(s):

Yuka Imanishi ◽

Masaki Hata ◽

Ryohei Matsukawa ◽

Atsushi Aoyagi ◽

Maiko Omi ◽

...

Keyword(s):

Stem Cells ◽

Bone Formation ◽

Extracellular Vesicles ◽

Dental Pulp ◽

Bone Defects ◽

Dental Pulp Stem Cells ◽

The Body ◽

Histological Observation ◽

Micro Ct ◽

Calvarial Bone

Abstract Background Extracellular vesicles (EVs) are known to be secreted by various cells. In particular, mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have tissue repair capacity and anti-inflammatory properties. Dental pulp stem cells (DPSCs), which are MSCs isolated from pulp tissue, are less invasive to the body than other MSCs and can be collected from young individuals. In this study, we investigated the efficacy of EVs secreted by DPSCs (DPSC-EVs) for bone formation. Methods DPSC-EVs were isolated from the cell culture medium of DPSCs. DPSC-EVs were unilaterally injected along with collagen (COL), beta-tricalcium phosphate (β-TCP) or hydroxyapatite (HA) into rat calvarial bone defects. The effects of DPSC-EVs were analyzed by micro-computed tomography (micro-CT) and histological observation. Results Micro-CT showed that administration of DPSC-EVs with the abovementioned scaffolds resulted in bone formation in the periphery of the defects. DPSC-EVs/COL specifically resulted in bone formation in the center of the defects. Histological observation revealed that DPSC-EVs/COL promoted new bone formation. Administration of DPSC-EVs/COL had almost the same effect on the bone defect site as transplantation of DPSCs/COL. Conclusions These results suggest that DPSC-EVs may be effective tools for bone tissue regeneration.

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Transplantation of Human Dental Pulp Stem Cells: Enhance Bone Consolidation in Mandibular Distraction Osteogenesis

Journal of Oral and Maxillofacial Surgery ◽

10.1016/j.joms.2013.05.016 ◽

2013 ◽

Vol 71 (10) ◽

pp. 1758.e1-1758.e13 ◽

Cited By ~ 19

Author(s):

Amera Alkaisi ◽

Abd Rashid Ismail ◽

Samarendra S. Mutum ◽

Zainal A. Rifin Ahmad ◽

Sam'an Masudi ◽

...

Keyword(s):

Stem Cells ◽

Distraction Osteogenesis ◽

Dental Pulp ◽

Dental Pulp Stem Cells ◽

Mandibular Distraction ◽

Bone Consolidation ◽

Mandibular Distraction Osteogenesis ◽

Human Dental Pulp

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Synthetic Scaffold/Dental Pulp Stem Cell (DPSC) Tissue Engineering Constructs for Bone Defect Treatment: An Animal Studies Literature Review

International Journal of Molecular Sciences ◽

10.3390/ijms21249765 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9765

Author(s):

Felice Lorusso ◽

Francesco Inchingolo ◽

Gianna Dipalma ◽

Francesca Postiglione ◽

Stefania Fulle ◽

...

Keyword(s):

Stem Cells ◽

Bone Formation ◽

Bone Defect ◽

Dental Pulp ◽

Animal Studies ◽

Meta Analysis ◽

Bone Defects ◽

New Bone Formation ◽

Synthetic Scaffold ◽

Bone Defect Treatment

Background: Recently a greater interest in tissue engineering for the treatment of large bone defect has been reported. The aim of the present systematic review and meta-analysis was to investigate the effectiveness of dental pulp stem cells and synthetic block complexes for bone defect treatment in preclinical in vivo articles. Methods: The electronic database and manual search was conducted on Pubmed, Scopus, and EMBASE. The papers identified were submitted for risk-of-bias assessment and classified according to new bone formation, bone graft characteristics, dental pulp stem cells (DPSCs) culture passages and amount of experimental data. The meta-analysis assessment was conducted to assess new bone formation in test sites with DPSCs/synthetic blocks vs. synthetic block alone. Results: The database search identified a total of 348 papers. After the initial screening, 30 studies were included, according to the different animal models: 19 papers on rats, 3 articles on rabbits, 2 manuscripts on sheep and 4 papers on swine. The meta-analysis evaluation showed a significantly increase in new bone formation in favor of DPSCs/synthetic scaffold complexes, if compared to the control at 4 weeks (Mean Diff: 17.09%, 95% CI: 15.16–18.91%, p < 0.01) and at 8 weeks (Mean Diff: 14.86%, 95% CI: 1.82–27.91%, p < 0.01) in rats calvaria bone defects. Conclusion: The synthetic scaffolds in association of DPSCs used for the treatment of bone defects showed encouraging results of early new bone formation in preclinical animal studies and could represent a useful resource for regenerative bone augmentation procedures

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