scholarly journals Sirt1 Promotes Osteogenic Differentiation and Increases Alveolar Bone Mass via Bmi1 Activation in Mice

2019 ◽  
Vol 34 (6) ◽  
pp. 1169-1181 ◽  
Author(s):  
Hua Wang ◽  
Zixuan Hu ◽  
Jun Wu ◽  
Yukun Mei ◽  
Qian Zhang ◽  
...  
2021 ◽  
Author(s):  
Rongrong Jiang ◽  
Miao Wang ◽  
Xiaobo Shen ◽  
Shuai Huang ◽  
Jianpeng Han ◽  
...  

Abstract Background: Periodontal disease, an oral disease characterized by loss of alveolar bone and progressive teeth loss, is the sixth major complication of diabetes. It is spreading worldwide as it is difficult to be cured. The insulin-like growth factor 1 receptor (IGF-1R) plays an important role in regulating functional impairment associated with diabetes. However, it is unclear whether IGF-1R expression in periodontal tissue is associated with periodontal bone tissue destruction in diabetic patients. SUMO modification has been reported in various diseases and are associated with an increasing number of biological processes, but previous studies have not focused on diabetic periodontitis.Methods: Periodontal membrane stem cells (PDLSCs) were isolated and cultured from healthy human obstructed teeth after extraction or adolescent orthodontic subtractive extraction. PDLSCs were cultured with medical 5% sterile glucose solution formulated as osteogenic differentiation induction solution with different glucose concentrations. The effects of different glucose concentrations on the osteogenic differentiation ability of PDLSCs were investigated at the genetic and cellular levels using staining assay, Western Blot, RT-PCR, Co-IP and cytofluorescence.Results: We found that SLUG, RUNX2 expression was decreased in PDLSCs cultured in high glucose osteogenic induction solution compared with normal glucose osteogenic induction solution. In addition, the IGF-1R expression levels, osteogenic differentiation and sumoylation of IGF-1R in PDLSCs cultured in high glucose osteogenic induction solution were not consistent with those cultured in normal glucose osteogenic induction solution.Conclusion: Our data demonstrated that SUMO1 modification of IGF-1R in high glucose environment inhibited osteogenic differentiation of PDLSCs by binding to SLUG, a key factor leading to periodontal bone tissue loss in diabetic patients. Thus we can maximize the control of multiple downstream damage signaling factors and bring new hope for periodontal tissue regeneration in diabetic patients.


Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1500
Author(s):  
Feng-Sheng Wang ◽  
Yu-Shan Chen ◽  
Jih-Yang Ko ◽  
Chung-Wen Kuo ◽  
Huei-Jing Ke ◽  
...  

Glucocorticoid provokes bone mass loss and fatty marrow, accelerating osteoporosis development. Bromodomain protein BRD4, an acetyl–histone-binding chromatin reader, regulates stem cell and tissue homeostasis. We uncovered that glucocorticoid inhibited acetyl Lys-9 at the histone 3 (H3K9ac)-binding Runx2 promoter and decreased osteogenic differentiation, whereas bromodomain protein 4 (BRD4) and adipocyte formation were upregulated in bone-marrow mesenchymal progenitor cells. BRD4 knockdown improved H3K9ac occupation at the Runx2 promoter and osteogenesis, but attenuated glucocorticoid-mediated adipocyte formation together with the unaffected H3K9ac-binding PPARγ2 promoter. BRD4 regulated epigenome related to fatty acid metabolism and the forkhead box P1 (Foxp1) pathway, which occupied the PPARγ2 promoter to modulate glucocorticoid-induced adipocytic activity. In vivo, BRD4 inhibitor JQ-1 treatment mitigated methylprednisolone-induced suppression of bone mass, trabecular microstructure, mineral acquisition, and osteogenic differentiation. Foxp1 signaling, marrow fat, and adipocyte formation in glucocorticoid-treated skeleton were reversed upon JQ-1 treatment. Taken together, glucocorticoid-induced H3K9 hypoacetylation augmented BRD4 action to Foxp1, which steered mesenchymal progenitor cells toward adipocytes at the cost of osteogenic differentiation in osteoporotic skeletons. BRD4 inhibition slowed bone mass loss and marrow adiposity. Collective investigations convey a new epigenetic insight into acetyl histone reader BRD4 control of osteogenesis and adipogenesis in skeleton, and highlight the remedial effects of the BRD4 inhibitor on glucocorticoid-induced osteoporosis.


2019 ◽  
Vol 30 (5) ◽  
pp. 722
Author(s):  
RiponMd Chowdhury ◽  
Saba Nasreen ◽  
DevaraNeela Sundara Venkata Ramesh ◽  
Rukmangada Thriveni ◽  
Amit Bayatnal ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rongrong Jiang ◽  
Miao Wang ◽  
Xiaobo Shen ◽  
Shuai Huang ◽  
Jianpeng Han ◽  
...  

Abstract Background Periodontal disease, an oral disease characterized by loss of alveolar bone and progressive teeth loss, is the sixth major complication of diabetes. It is spreading worldwide as it is difficult to be cured. The insulin-like growth factor 1 receptor (IGF-1R) plays an important role in regulating functional impairment associated with diabetes. However, it is unclear whether IGF-1R expression in periodontal tissue is related to alveolar bone destruction in diabetic patients. SUMO modification has been reported in various diseases and is associated with an increasing number of biological processes, but previous studies have not focused on diabetic periodontitis. This study aimed to explore the role of IGF-1R in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in high glucose and control the multiple downstream damage signal factors. Methods PDLSCs were isolated and cultured after extraction of impacted teeth from healthy donors or subtractive orthodontic extraction in adolescents. PDLSCs were cultured in the osteogenic medium with different glucose concentrations prepared by medical 5% sterile glucose solution. The effects of different glucose concentrations on the osteogenic differentiation ability of PDLSCs were studied at the genetic and cellular levels by staining assay, Western Blot, RT-PCR, Co-IP and cytofluorescence. Results We found that SNAI2, RUNX2 expression decreased in PDLSCs cultured in high glucose osteogenic medium compared with that in normal glucose osteogenic medium, which were osteogenesis-related marker. In addition, the IGF-1R expression, sumoylation of IGF-1R and osteogenic differentiation in PDLSCs cultured in high glucose osteogenic medium were not consistent with those cultured in normal glucose osteogenic medium. However, osteogenic differentiation of PDLCSs enhanced after adding IGF-1R inhibitors to high glucose osteogenic medium. Conclusion Our data demonstrated that SUMO1 modification of IGF-1R inhibited osteogenic differentiation of PDLSCs by binding to SNAI2 in high glucose environment, a key factor leading to alveolar bone loss in diabetic patients. Thus we could maximize the control of multiple downstream damage signaling factors and bring new hope for alveolar bone regeneration in diabetic patients.


Bone ◽  
2006 ◽  
Vol 39 (3) ◽  
pp. 552-564 ◽  
Author(s):  
T. Savage ◽  
T. Bennett ◽  
Y.-F. Huang ◽  
P.L. Kelly ◽  
N.E. Durant ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Satoshi Komasa ◽  
Tetsuji Kusumoto ◽  
Yoichiro Taguchi ◽  
Hiroshi Nishizaki ◽  
Tohru Sekino ◽  
...  

Titanium alloys are the most frequently used dental implants partly because of the protective oxide coating that spontaneously forms on their surface. We fabricated titania nanosheet (TNS) structures on titanium surfaces by NaOH treatment to improve bone differentiation on titanium alloy implants. The cellular response to TNSs on Ti6Al4V alloy was investigated, and the ability of the modified surfaces to affect osteogenic differentiation of rat bone marrow cells and increase the success rate of titanium implants was evaluated. The nanoscale network structures formed by alkali etching markedly enhanced the functions of cell adhesion and osteogenesis-related gene expression of rat bone marrow cells. Other cell behaviors, such as proliferation, alkaline phosphatase activity, osteocalcin deposition, and mineralization, were also markedly increased in TNS-modified Ti6Al4V. Our results suggest that titanium implants modified with nanostructures promote osteogenic differentiation, which may improve the biointegration of these implants into the alveolar bone.


2011 ◽  
Vol 22 (6) ◽  
pp. 878 ◽  
Author(s):  
Karishma Mahajan ◽  
Nina Shenoy ◽  
Amitha Ramesh ◽  
Biju Thomas ◽  
Rahul Bhandary

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1134 ◽  
Author(s):  
Alexander Patera Nugraha ◽  
Ida Bagus Narmada ◽  
Diah Savitri Ernawati ◽  
Aristika Dinaryanti ◽  
Eryk Hendrianto ◽  
...  

Background: Alveolar bone defect regeneration has long been problematic in the field of dentistry. Gingival stromal progenitor cells (GSPCs) offer a promising solution for alveolar bone regeneration. In order to optimally differentiate and proliferate progenitor cells, growth factors (GFs) are required. Platelet rich fibrin (PRF) has many GFs and can be easily manufactured. Core-binding factor subunit-α1 (CBF-α1) constitutes a well-known osteogenic differentiation transcription factor in SPCs. Sox9, as a chondrogenic transcription factor, interacts and inhibits CBF-α1, but its precise role in direct in vitro osteogenesis remains unknown. GSPCs cultured in vitro in PRF to optimally stimulate osteogenic differentiation has been largely overlooked. The aim of this study was to analyze GSPCs cultured in PRF osteogenic differentiation predicted by CBF-α1/Sox9. Methods: This study used a true experimental with post-test only control group design and random sampling. GPSCs isolated from the lower gingiva of four healthy, 250-gram, 1-month old, male Wistar rats (Rattus Novergicus) were cultured for two weeks, passaged every 4-5 days. GSPCs in passage 3-5 were cultured in five M24 plates (N=108; n=6/group) for Day 7, Day 14, and Day 21 in three different mediums (control negative group: αModified Eagle Medium; control positive group: High Glucose-Dulbecco’s Modified Eagle Medium (DMEM-HG) + osteogenic medium; Treatment group: DMEM-HG + osteogenic medium + PRF). CBF-α1 and Sox9 were examined with ICC monoclonal antibody. A one-way ANOVA continued with Tukey HSD test (p<0.05) based on Kolmogorov–Smirnov and Levene's tests (p>0.05) was performed. Results: The treatment group showed the highest CBF-α1/Sox9 ratio (16.00±3.000/14.33±2.517) on Day 7, while the lowest CBF-α1/Sox9 ratio (3.33±1.528/3.67±1.155) occurred in the control negative group on Day 21, with significant difference between the groups (p<0.05). Conclusion: GSPCs cultured in PRF had potential osteogenic differentiation ability predicted by the CBF-α1/sox9 ratio.


2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Qingyuan Guo ◽  
Ying Liu ◽  
Renhao Sun ◽  
Fang Yang ◽  
Pengyan Qiao ◽  
...  

Abstract The relationship between mechanical force and alveolar bone remodeling is an important issue in orthodontics because tooth movement is dependent on the response of bone tissue to the mechanical force induced by the appliances used. Mechanical cyclical stretch plays an essential role in the cell osteogenic differentiation involved in bone remodeling. However, the underlying mechanisms are unclear, particularly the molecular pathways regulated by mechanical stimulation. In the present study, we reported a dynamic change of p21 level in response to mechanical cyclical stretch, and shRNA-p21 in bone marrow mesenchymal stem cells (BMSCs) induced osteogenic differentiation. The mechanism was mediated through TWIST/E2A/p21 axis. These results supported the mechanical stimulation-induced osteogenic differentiation is negatively regulated by p21.


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