Journal of Stem Cells Research Development & Therapy Category: Medical Type: Short Review
LncRNAs Regulate the PDLSCs Osteogenic Differentiation in Periodontitis
- Yuerong Xu1, Zuolin Jin1*, Mingming Zhang2*
- 1 State Key Laboratory Of Military Stomatology And National Clinical Research Center For Oral Diseases, Department Of Orthodontics, School Of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi 710032, China
- 2 Department Of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
*Corresponding Author:Zuolin Jin
State Key Laboratory Of Military Stomatology And National Clinical Research Center For Oral Diseases, Department Of Orthodontics, School Of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi 710032, China
Department Of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
Received Date: Oct 16, 2019 Accepted Date: Nov 05, 2019 Published Date: Nov 12, 2019
Mesenchymal Stem Cells (MSCs) have been used for periodontal regeneration. MSCs first discovered in the bone marrow have the potential to differentiate into many types of cells, including osteoblasts, chondrocytes, myocytes and adipocytes . Periodontal Ligament Stem Cells (PDLSCs) were first isolated from the periodontal ligament of third molars extracted from 25 patients by Seo et al., in 2004 . PDLSCs can differentiate into adipocytes or osteoblasts, depending on the different culture conditions, and can contribute to the regeneration of periodontal ligament in vivo, thus, is considered to be a seed for periodontal regeneration.
In the human body, there are specific micro-environments that are suit for the proliferation and differentiation of stem cells, called stem cell nests . Inflammation, as an influencing factor affecting the homeostasis of the nest, could change the function of various stem cells; therefore have a negative effect on tissue regeneration . In 2011 Liu N et al.,  first discovered that pPDLSCs (Periodontal Mesenchymal Stem Cells from periodontitis patients), compared to hPDLSCs (Periodontal Mesenchymal Stem Cells from healthy microenvironment), had enhanced proliferative capacity but reduced osteogenic differentiation ability. This explained why the PDLSCs-based treatment could hardly achieve periodontal regeneration. Therefore, currently improving the multiple differentiation ability of PPDLSCs and repairing damaged periodontal tissues is still challenging.
Long non-coding RNA (LncRNA) is one of non-coding RNAs, with the transcript length more than 200 nt. This type of RNA is transcribed in large quantities in cells, yet has been considered to be transcriptional "noise" in early studies, due to its lack of coding function. With the discovery of lncRNA-HOTAIR in 2007, the function of lncRNA has become clearer. Based on their structural features and cellular location, lncRNAs can be divided into five subcategories: antisense, long intergenic non-coding RNA (lincRNA), sense overlap, sense introns and processed transcripts . Due to the flexibility of RNA, lncRNA can be folded into different unique secondary conformations, including the DNA binding domain, the RNA binding domain and the protein binding domain, enabling it to form a broad regulatory network with DNA, RNA particles and protein complexes [9-13]. LncRNA has been shown to affect transcription and post-transcriptional gene expression through a variety of mechanisms, for instances, by modulating chromatin remodeling, acting as competitive endogenous RNA (ceRNA), regulating mRNA stability or recruiting scaffold proteins [14-19]. This information helps to clarify their key role in normal and disease development. It is clear that lncRNA can regulate gene expression at epigenetic , transcription  and post-transcriptional  levels, and participate in X chromosome silencing, genomic imprinting. And a variety of important regulatory processes such as chromatin modification, transcriptional activation and inhibition, nuclear transport, etc., are pathophysiologically relevent.
The major mechanisms of lncRNA action are based on RNA and protein regulation, RNA and RNA interactions, and RNA-DNA interactions . RNA-protein complexes can be formed, such as lncRNPs, to further mediate the correct localization of chromatin regulatory proteins or to recruit functional proteins with different protein interaction domains [24,25]. LncRNA is also involved in the regulation of pre-mRNA splicing, RNA editing, mRNA stability control, translational activation and can function as miRNA sponge . In addition, lncRNAs play a key role in regulating biological processes by targeting RNA-DNA triplex targeting specific DNA sequences . In recent years, lncRNA has been shown to affect the differentiation of PDLSCs, and certain lncRNAs can modulate the osteogenesis of PDLSCs . Existing studies have demonstrated that lncRNA has two modes of action in osteogenic differentiation of PDLSCs (lncRNA-miRNA mode and RBP mode).
A systematic characterization integrating 22 studies of periodontal regeneration using MSCs in animal models was performed. Apparently, MSCs have regenerative potential in animal models of periodontal defects, but there are differences in the reproductive potential of MSCs in different studies . In addition, human studies have used PDLSC to achieve periodontal regeneration . We found that LncRNA-TWIST1 promoted osteogenic differentiation both in PPDLSCs and in HPDLSCs by inhibiting TWIST1 expression . Periodontitis induces the tooth loss by destroying the supporting structures of tooth. Chen et al showed the cell-based periodontal therapy is safe and efficient . We propose that lncRNAs could be used to repair the damaged PDLSCs in periodontitis. It is expected that in-depth study of the role of lncRNA in osteogenic differentiation of PDLSCs would offer more insights into the mechanism of periodontal regeneration and for developing more effective therapeutic strategies to treat the diseases.
The present review summarizes the potential roles of lncRNAs in the PDLSCs osteogenic differentiation in periodontitis. Most of the studies proved that the lncRNAs regulate the PDLSCs osteogenic differentiation in periodontitis, but only few of them investigated the molecular mechanisms of lncRNAs on regulating PDLSCs osteogenic differentiation process. In summary, lncRNAs were proved to regulate the PDLSCs osteogenic differentiation in periodontitis by multiple regulatory effects, including periodontal inflammation and oxidative stress. Furthermore, miRNAs and proteins have been proved to be the direct targets of lncRNAs. However, the lncRNAs which could regulate the PDLSCs osteogenic differentiation in periodontitis are very limited. In the future study, the researchers should study deeply the regulative effects of lncRNAs and whether the lncRNAs could regulate the other cells such as macrophage and periodontal cells. Furthermore, natural lncRNAs modulators may be used for the prevention and treatment of periodontitis.
CONFLICT OF INTEREST
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Citation:Xu Y, Jin Z, Zhang M (2019) LncRNAs Regulate the PDLSCs Osteogenic Differentiation in Periodontitis. J Stem Cell Res Dev Ther 5: 021.
Copyright: © 2019 Yuerong Xu, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.