scholarly journals lncRNA HHIP-AS1 Promotes the Osteogenic Differentiation Potential and Inhibits the Migration Ability of Periodontal Ligament Stem Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qianyi Qin ◽  
Haoqing Yang ◽  
Chen Zhang ◽  
Xiao Han ◽  
Jing Guo ◽  
...  

Alveolar bone remodeling under orthodontic force is achieved by periodontal ligament stem cells (PDLSCs), which are sensitive to mechanical loading. How to regulate functions of PDLSCs is a key issue in bone remodeling during orthodontic tooth movement. This study is aimed at investigating the roles of lncRNA Hedgehog-interacting protein antisense RNA 1 (HHIP-AS1) in the functional regulation of PDLSCs. First, HHIP-AS1 expression was downregulated in PDLSCs under continuous compressive pressure. Then, we found that the alkaline phosphatase activity, in vitro mineralization, and expression levels of bone sialoprotein, osteocalcin, and osterix were increased in PDLSCs by HHIP-AS1. The results of scratch migration and transwell chemotaxis assays revealed that HHIP-AS1 inhibited the migration and chemotaxis abilities of PDLSCs. In addition, the RNA sequencing data showed that 356 mRNAs and 14 lncRNAs were upregulated, including receptor tyrosine kinase-like orphan receptor 2 and nuclear-enriched abundant transcript 1, while 185 mRNAs and 6 lncRNAs were downregulated, including fibroblast growth factor 5 and LINC00973, in HHIP-AS1-depleted PDLSCs. Bioinformatic analysis revealed several biological processes and signaling pathways related to HHIP-AS1 functions, including the PI3K-Akt signaling pathway and JAK-STAT signaling pathway. In conclusion, our findings indicated that HHIP-AS1 was downregulated in PDLSCs under compressive pressure, and it promoted the osteogenic differentiation potential and inhibited the migration and chemotaxis abilities of PDLSCs. Thus, HHIP-AS1 may be a potential target for accelerating tooth movement during orthodontic treatment.

Author(s):  
Nan Jiang ◽  
Danqing He ◽  
Yushi Ma ◽  
Junxiang Su ◽  
Xiaowen Wu ◽  
...  

Autophagy, a lysosomal degradation pathway, serves as a protective cellular mechanism in maintaining cell and tissue homeostasis under mechanical stimulation. As the mechanosensitive cells, periodontal ligament stem cells (PDLSCs) play an important role in the force-induced inflammatory bone remodeling and tooth movement process. However, whether and how autophagy in PDLSCs influences the inflammatory bone remodeling process under mechanical force stimuli is still unknown. In this study, we found that mechanical force stimuli increased the expression of the autophagy protein LC3, the number of M1 macrophages and osteoclasts, as well as the ratio of M1/M2 macrophages in the compression side of the periodontal ligament in vivo. These biological changes induced by mechanical force were repressed by the application of an autophagy inhibitor 3-methyladenine. Moreover, autophagy was activated in the force-loaded PDLSCs, and force-stimulated PDLSC autophagy further induced M1 macrophage polarization in vitro. The macrophage polarization could be partially blocked by the administration of autophagy inhibitor 3-methyladenine or enhanced by the administration of autophagy activator rapamycin in PDLSCs. Mechanistically, force-induced PDLSC autophagy promoted M1 macrophage polarization via the inhibition of the AKT signaling pathway. These data suggest a novel mechanism that force-stimulated PDLSC autophagy steers macrophages into the M1 phenotype via the AKT signaling pathway, which contributes to the inflammatory bone remodeling and tooth movement process.


2010 ◽  
Vol 31 (2) ◽  
pp. 117-124 ◽  
Author(s):  
Feng Pan ◽  
Rui Zhang ◽  
Guang Wang ◽  
Yin Ding

The existence of PDLSCs [PDL (periodontal ligament) stem cells] in PDL has been identified and such cells may function in periodontal reconstruction, including bone formation. Oestrogens/ERs (oestrogen receptors; ERα and ERβ) exert important effects in bone formation, however, the relationship between ERs and PDLSCs has not been established. In the present study, PDLSCs were isolated and assays for detecting stem-cell biomarkers and multipotential differentiation potential confirmed the validity of human PDLSCs. The results of RT–PCR (reverse transcription–PCR) and Western blotting showed that ERα and ERβ were expressed at higher levels in PDLSCs as compared with PDLCs (PDL cells), and 17β-oestradiol obviously induced the osteogenic differentiation of PDLSCs in vitro. Furthermore, a pan-ER inhibitor or lentivirus-mediated siRNA (small interfering RNA) targeting ERα or ERβ blocked the oestrogen-induced osteogenic differentiation of PDLSCs. The results indicate that both ERα and ERβ were involved in the process of osteogenic differentiation of PDLSCs.


2019 ◽  
Author(s):  
Zhuo Wang ◽  
Yuanliang Huang ◽  
Luanjun Tan

Abstract Backgrounds: Long non-coding RNAs (lncRNAs) have been widely known to have an appreciable effect in physiology and pathology. In tooth regeneration, periodontal ligament stem cells (PDLSCs) are regarded as a key effector, whereas, how lncRNA acts in the osteogenic differentiation of PDLSCs have not been completely understood. This study aims to find out the relationship between lncRNA DANCR and the proliferation and osteogenic differentiation of PDLSCs. Method: Microarray was used to observe the different expression of lncRNAs in differentiated and undifferentiated PDLSCs. And then osteogenic-related lncRNA, DNACR was screened out. To explore its effects on proliferation and osteogenic differentiation by constructing an overexpression and inhibition model. qRT-PCR was used to detect the mRNA expression of osteogenesis related genes. MTT assay was performed to assess the effects of DNACR on cell growth curve. To quantify the effects of DNACR on osteogenic differentiation of PDLCs, ALP staining and alizarin red was performed in basic culture medium and osteogenic medium. Data were statistically processed. Results: Compared with the undifferentiated PDLSCs, the alizarin red staining level was higher in differentiated PDLSCs. And the expressions of osteogenic differentiation marker genes Runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and bone morphogenetic protein (BMP-2) were significantly increased in the differentiated PDLSCs. Furthermore, we noticed that comparing with control groups, the expression of LncRNA DANCR decreases markedly in osteogenically induced PDLSCs. DANCR promoted proliferation of PDLSCs, as evidenced by cell viability. Further investigation has proven that the downregulation of DANCR shows in the calcium sediment forming, alkaline phosphatase (ALP) activation and some osteogenic-related gene markers’ upregulation including Runx2, OCN and BMP-2, which finally results in the osteogenic differentiation of PDLSCs following the transfection and induction. Conversely, DANCR upregulation was shown to repress the osteogenic differentiation potential of PDLSCs. Conclusions: The osteogenic differentiation of PDLSCs has proven to related to the down regulation of lncRNA DANCR. And this paper throws light on the effects of DANCR in the process of PDLSCs’ osteogenic differentiation.


2019 ◽  
Author(s):  
Zhuo Wang ◽  
Yuanliang Huang ◽  
Luanjun Tan

Abstract Backgrounds: Long non-coding RNAs (lncRNAs) have been widely known to have an appreciable effect in physiology and pathology. In tooth regeneration, periodontal ligament stem cells (PDLSCs) are regarded as a key effector, whereas, how lncRNA acts in the osteogenic differentiation of PDLSCs haven’t been completely understood. This study aims to find out the relationship between lncRNA DANCR and the proliferation and osteogenic differentiation of PDLSCs. Results: Compared with the undifferentiated PDLSCs, the alizarin red staining level was higher in differentiated PDLSCs. And the expressions of osteogenic differentiation marker genes Runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and bone morphogenetic protein (BMP-2) were significantly increased in the differentiated PDLSCs. Furthermore, we noticed that comparing with control groups, the expression of LncRNA DANCR decreases markedly in osteogenically induced PDLSCs. DANCR promoted proliferation of PDLSCs, as evidenced by cell viability. Further investigation has proven that the downregulation of DANCR shows in the calcium sediment forming, alkaline phosphatase (ALP) activation and some osteogenic-related gene markers’ upregulation including Runx2, OCN and BMP-2, which finally results in the osteogenic differentiation of PDLSCs following the transfection and induction. Conversely, DANCR upregulation was shown to repress the osteogenic differentiation potential of PDLSCs. Conclusions: The osteogenic differentiation of PDLSCs has proven to related to the down regulation of lncRNA DANCR. And this paper throws light on the effects of DANCR in the process of PDLSCs’ osteogenic differentiation.


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