Stem cells in the periodontal ligament differentiated into osteogenic, fibrogenic and cementogenic lineages for the regeneration of the periodontal complex

Jin, Liu; Zhao, Zeqing; Ruan, Jianping; Weir, Michael D.; Ma, Tao; Ren, Ke; Schneider, Abraham; Oates, Thomas W.; Li, Ang; Zhao, Liang; Xu, Hockin H.K.

doi:10.1016/j.jdent.2019.103259

Cited by 61 publications

(65 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The hPDLSCs were isolated from periodontal ligament (PDL) tissues of extracted human adult premolars as previously reported (Liu et al., 2020). The procedures were approved by the Institutional Review Board of the University of Maryland, Baltimore.…”

Section: Methodsmentioning

confidence: 99%

Antibacterial calcium phosphate cement with human periodontal ligament stem cell‐microbeads to enhance bone regeneration and combat infection

Qiu

Huang

Jin

et al. 2021

J Tissue Eng Regen Med

Self Cite

View full text Add to dashboard Cite

Infectious bone defects remain a significant challenge in orthopedics and dentistry. Calcium phosphate cement (CPC) have attracted significant interest in use as local drug delivery system, which with great potential to control release of antibiotics for the treatment of infectious bone defects. Within the current study, a novel antibacterial scaffold of chitosan‐reinforced calcium phosphate cement delivering doxycycline hyclate (CPCC + DOX) was developed. Furthermore, the capacity of CPCC + DOX scaffolds for bone regeneration was enhanced by the human periodontal ligament stem cells (hPDLSCs) encapsulated in alginate beads. CPCC + DOX scaffolds were fabricated to contain different concentrations of DOX. Flexural strength of CPCC + DOX ranged from 5.56 ± 0.70 to 6.2 ± 0.72 MPa, which exceeded the reported strength of cancellous bone. Scaffolds exhibited continual DOX release, reaching 80% at 21 days. Scaffold with 5 mg/ml DOX (CPCC + DOX5mg) had a strong antibacterial effect, with a 4‐log colony forming unit reduction against S. aureus and P. gingivalis. The proliferation and osteogenic differentiation of hPDLSCs encapsulated in alginate hydrogel microbeads were investigated in culture with CPCC + DOX scaffolds. CPCC + DOX5mg had no negative effect on proliferation of hPDLSCs. Alkaline phosphatase activity, mineral synthesis, and osteogenic gene expressions for CPCC + DOX5mg group were much higher than control group. DOX did not compromise the osteogenic induction. In summary, the novel CPCC + DOX scaffold exhibited excellent mechanical properties and strong antibacterial activity, while supporting the proliferation and osteogenic differentiation of hPDLSCs. The CPCC + DOX + hPDLSCs construct is promising to enhance bone regeneration and combat bone infections in dental, craniofacial, and orthopedic applications.

show abstract

Section: Methodsmentioning

confidence: 99%

Antibacterial calcium phosphate cement with human periodontal ligament stem cell‐microbeads to enhance bone regeneration and combat infection

Qiu

Huang

Jin

et al. 2021

J Tissue Eng Regen Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, the existence of PDLSCs was not revealed until 2004 when Seo et al 4 identified and named them. Subsequently, the potential of PDLSCs to differentiate into osteogenic, fibrogenic, and cementogenic lineages and form bone‐PDL‐cementum complexes was discovered 5 . These findings paved the way for the real‐world application of stem cell–based therapies for periodontal disease.…”

Section: Introductionmentioning

confidence: 98%

MiR‐153‐3p inhibits osteogenic differentiation of periodontal ligament stem cells through KDM6A‐induced demethylation of H3K27me3

Jiang

Jia

2020

J of Periodontal Research

View full text Add to dashboard Cite

Background and objective Periodontal ligament stem cells (PDLSCs) have potential for osteogenic differentiation and show a great foreground in treating bone diseases. Histone three lysine 27 (H3K27) demethylase lysine demethylase 6A (KDM6A) is a critical epigenetic modifier and plays an important role in regulating osteogenic differentiation. Multiple microRNAs have been found to play important roles in osteogenesis. The aim of this study was to explore the mechanisms underlying the roles of miR‐153‐3p and KDM6A in PDLSC osteogenesis. Methods The levels of the osteogenic markers alkaline phosphatase (ALP), runt‐related transcription factor 2 (Runx2), and osteopontin (OPN) were measured by western blotting. Osteoblast activity and mineral deposition were detected by ALP and Alizarin red S (ARS) staining. The levels of miR‐153‐3p and KDM6A were measured by quantitative real‐time PCR (qRT‐PCR). A luciferase reporter assay was used to confirm the interaction between KDM6A and miR‐153‐3p. Gain‐of‐function and loss‐of‐function assays were performed to identify the roles of miR‐153‐3p and KDM6A in the osteogenic differentiation of PDLSCs. Results In osteogenic PDLSCs, the expression of KDM6A, ALP, Runx2, and OPN was upregulated, whereas that of miR‐153‐3p was downregulated. miR‐153‐3p downregulation or KDM6A overexpression promoted the osteogenic differentiation of PDLSCs, as demonstrated by increases in ALP activity, matrix mineralization, and ALP, Runx2, and OPN expression. KDM6A was confirmed to be a target of miR‐153‐3p, and KDM6A overexpression reversed the inhibitory effect of miR‐153‐3p mimic on PDLSC osteogenesis. KDM6A promoted ALP, Runx2, and OPN expression through the demethylation of H3K27me3 on the promoter regions of these genes. Conclusion miR‐153‐3p inhibited PDLSC osteogenesis by targeting KDM6A and inhibiting ALP, Runx2, and OPN transcription. These findings provide latent hope for PDLSCs application in periodontal therapy.

show abstract

“…When cultivated under osteogenic conditions, PDLCs differentiate into osteoblast-like cells in vitro (Seo et al, 2004;Gay et al, 2007;Liu et al, 2020). This is associated with upregulation of osteoblast-related genes, such as Runtrelated transcription factor 2 (RUNX2), which encodes for an essential and initiating transcription factor required for osteoblastogenesis (Komori et al, 1997;Enomoto et al, 2003;Li et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

DNMT1 Inhibitor Restores RUNX2 Expression and Mineralization in Periodontal Ligament Cells

Assis

Schmidt

Racca

et al. 2021

DNA and Cell Biology

View full text Add to dashboard Cite

Periodontal ligament cells (PDLCs) have well documented osteogenic potential; however, this commitment can be highly heterogenous, limiting their applications in tissue regeneration. In this study, we use PDLC populations characterized by high and low osteogenic potential (h-PDLCs and l-PDLCs, respectively) to identify possible sources of such heterogeneity and to investigate whether the osteogenic differentiation can be enhanced by epigenetic modulation. In h-PDLCs, low basal expression levels of pluripotency markers (NANOG, OCT4), DNA methyltransferases (DNMT1, DNMT3B), and enzymes involved in active DNA demethylation (TET1, TET3) were prerequisite to high osteogenic potential. Furthermore, these genes were downregulated upon early osteogenesis, possibly allowing for the increase in expression of the key osteogenic transcription factors, Runt-related transcription factor 2 (RUNX2) and SP7, and ultimately, mineral nodule formation. l-PDLCs appeared locked in the multipotent state and this was further enhanced upon early osteogenic stimulation, correlating with low RUNX2 expression and impaired mineralization. Further upregulation of DNMTs was also evident, while pretreatment with RG108, the DNMTs' inhibitor, enhanced the osteogenic program in l-PDLCs through downregulation of DNMTs, increased RUNX2 expression and nuclear localization, accelerated expression of osteogenic markers, and increased mineralization. These findings point toward the role of DNMTs and Ten Eleven Translocations (TETs) in osteogenic commitment and support application of epigenetic approaches to modulate biomineralization in PDLCs.

show abstract

Stem cells in the periodontal ligament differentiated into osteogenic, fibrogenic and cementogenic lineages for the regeneration of the periodontal complex

Cited by 61 publications

References 52 publications

Antibacterial calcium phosphate cement with human periodontal ligament stem cell‐microbeads to enhance bone regeneration and combat infection

Antibacterial calcium phosphate cement with human periodontal ligament stem cell‐microbeads to enhance bone regeneration and combat infection

MiR‐153‐3p inhibits osteogenic differentiation of periodontal ligament stem cells through KDM6A‐induced demethylation of H3K27me3

DNMT1 Inhibitor Restores RUNX2 Expression and Mineralization in Periodontal Ligament Cells

Contact Info

Product

Resources

About