Dysfunction of MiR-148a-NRP1 Functional Axis Suppresses Osteogenic Differentiation of Periodontal Ligament Stem Cells Under Inflammatory Microenvironment

Bao, Liuliu; Zhang, Xiang; Xu, Yingbin; Wang, Miao; Song, Yihua; Gu, Yongchun; Zheng, Ya; Xiao, Jingwen; Wang, Yuzhe; Zhou, Qiao; Qian, Jie; Lv, Yi; Ji, Lujun; Feng, Xiaoxing

doi:10.1089/cell.2019.0026

Cited by 16 publications

(11 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inhibition of EZH2 ameliorated the BMP2-mediated osteoblast differentiation of the progenitor cells and induction of stereotyped osteoblast maturation [ 37 ]. Osteogenic regeneration is an important process of the periodontal tissue regeneration, and many studies have shown that the osteogenic differentiation ability of PDLSCs is significantly reduced under the inflammatory conditions [ 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

EZH2 Regulates Lipopolysaccharide-Induced Periodontal Ligament Stem Cell Proliferation and Osteogenesis through TLR4/MyD88/NF-κB Pathway

Wang

Tian

Zhang

et al. 2021

Stem Cells International

View full text Add to dashboard Cite

Background. Periodontitis induced by bacteria especially Gram-negative bacteria is the most prevalent chronic inflammatory disease worldwide. Emerging evidence supported that EZH2 plays a significant role in the inflammatory response of periodontal tissues. However, little information is available regarding the underlying mechanism of EZH2 in periodontitis. This study is aimed at determining the potential role and underlying mechanism of EZH2 in periodontitis. Methods. The protein levels of EZH2, H3K27ME, p-p65, p-IKB, TLR4, MyD88, Runx2, and OCN were examined by western blot assay. Proliferation was evaluated by CCK8 assay. The levels of TNFα, IL1β, and IL6 were detected by ELISA assay. Migration was detected by wound healing assay. The distribution of p65 was detected by immunofluorescence. The formation of mineralized nodules was analyzed using alizarin red staining. Results. LPS stimulation significantly promoted EZH2 and H3K27me3 expression in primary human periodontal ligament stem cells (PDLSCs). Targeting EZH2 prevented LPS-induced upregulation of the inflammatory cytokines and inhibition of cell proliferation and migration. Furthermore, EZH2 knockdown attenuated the TLR4/MyD88/NF-κB signaling to facilitate PDLSC osteogenesis. Conclusions. Modulation of the NF-κB pathway through the inhibition of EZH2 may offer a new perspective on the treatment of chronic apical periodontitis.

show abstract

Section: Discussionmentioning

confidence: 99%

EZH2 Regulates Lipopolysaccharide-Induced Periodontal Ligament Stem Cell Proliferation and Osteogenesis through TLR4/MyD88/NF-κB Pathway

Wang

Tian

Zhang

et al. 2021

Stem Cells International

View full text Add to dashboard Cite

show abstract

“…The osteoblast differentiation process was performed as described in our previous study [ 24 ]. The P4 generation of PDLSCs were used as the study subject and inoculated in 6-well culture plates at a density of 3000 cells/cm 2 , and the osteogenic differentiation induction medium (50 µg/mL ascorbic acid, 10 mM sodium glycerophosphate, and 1.0 µg/mL dexamethasone) was configured with different glucose concentrations of complete culture medium (5.…”

Section: Methodsmentioning

confidence: 99%

SUMO1 modification of IGF-1R combining with SNAI2 inhibited osteogenic differentiation of PDLSCs stimulated by high glucose

et al. 2021

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Inhibition of miR-214 in PDLSCs can decrease osteogenic differentiation by targeting activating transcription factor 4 and regulating the Wnt/β-catenin signaling pathway[ 128 , 129 ]. Downregulation of miR-148a in PDLSCs rescues the inhibition of osteogenesis triggered by LPS stimulation[ 130 ]. miR-22 and miR-17 promote osteogenesis of PDLSCs by inhibiting HDAC6 and HDAC9 expression, respectively, the latter under inflammatory conditions[ 131 , 132 ].…”

Section: Multiple Factors Influencing the Odontogenic/osteogenic Differentiation Of Dmscsmentioning

confidence: 99%

Multidifferentiation potential of dental-derived stem cells

Yin¹,

Luo²,

Feng³

et al. 2021

WJSC

View full text Add to dashboard Cite

Tooth-related diseases and tooth loss are widespread and are a major public health issue. The loss of teeth can affect chewing, speech, appearance and even psychology. Therefore, the science of tooth regeneration has emerged, and attention has focused on tooth regeneration based on the principles of tooth development and stem cells combined with tissue engineering technology. As undifferentiated stem cells in normal tooth tissues, dental mesenchymal stem cells (DMSCs), which are a desirable source of autologous stem cells, play a significant role in tooth regeneration. Researchers hope to reconstruct the complete tooth tissues with normal functions and vascularization by utilizing the odontogenic differentiation potential of DMSCs. Moreover, DMSCs also have the ability to differentiate towards cells of other tissue types due to their multipotency. This review focuses on the multipotential capacity of DMSCs to differentiate into various tissues, such as bone, cartilage, tendon, vessels, neural tissues, muscle-like tissues, hepatic-like tissues, eye tissues and glands and the influence of various regulatory factors, such as non-coding RNAs, signaling pathways, inflammation, aging and exosomes, on the odontogenic/osteogenic differentiation of DMSCs in tooth regeneration. The application of DMSCs in regenerative medicine and tissue engineering will be improved if the differentiation characteristics of DMSCs can be fully utilized, and the factors that regulate their differentiation can be well controlled.

show abstract

Dysfunction of MiR-148a-NRP1 Functional Axis Suppresses Osteogenic Differentiation of Periodontal Ligament Stem Cells Under Inflammatory Microenvironment

Cited by 16 publications

References 32 publications

EZH2 Regulates Lipopolysaccharide-Induced Periodontal Ligament Stem Cell Proliferation and Osteogenesis through TLR4/MyD88/NF-κB Pathway

EZH2 Regulates Lipopolysaccharide-Induced Periodontal Ligament Stem Cell Proliferation and Osteogenesis through TLR4/MyD88/NF-κB Pathway

SUMO1 modification of IGF-1R combining with SNAI2 inhibited osteogenic differentiation of PDLSCs stimulated by high glucose

Multidifferentiation potential of dental-derived stem cells

Contact Info

Product

Resources

About