Identification and characterization of circular RNAs involved in mechanical force‐induced periodontal ligament stem cells

2018 ◽  
Vol 234 (7) ◽  
pp. 10166-10177 ◽  
Author(s):  
Hong Wang ◽  
Cheng Feng ◽  
Ye Jin ◽  
Wanye Tan ◽  
Fulan Wei
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.


Oral Diseases ◽  
2020 ◽  
Author(s):  
Hong Wang ◽  
Cheng Feng ◽  
Mengying Li ◽  
Zijie Zhang ◽  
Jiani Liu ◽  
...  

2021 ◽  
Vol 25 (4) ◽  
pp. 295
Author(s):  
BhavnaJha Kukreja ◽  
KishoreGajanan Bhat ◽  
Pankaj Kukreja ◽  
VijayMahadev Kumber ◽  
Rajkumar Balakrishnan ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Jia Liu ◽  
Qiang Li ◽  
Shiyu Liu ◽  
Jie Gao ◽  
Wen Qin ◽  
...  

During orthodontic treatment, periodontium remodeling of periodontitis patients under mechanical force was abnormal. We have previously confirmed the function impairment of periodontal ligament stem cells (PDLSCs) in the periodontitis microenvironment which might be involved in this pathological process. However, the response of PDLSCs in periodontitis microenvironment to mechanical force remains unclear. Therefore, in the present study, we introduced a Flexcell tension apparatus and investigated the response of PDLSCs obtained from periodontal tissues of periodontitis patients (PPDLSCs) and of those obtained from healthy periodontal tissues (HPDLSCs) to different magnitudes of static mechanical strain (SMS). PPDLSCs showed increased proliferation, decreased osteogenic activity, activated osteoclastogenesis, and greater secretion of inflammatory cytokines. Different magnitudes of SMS exerted distinct effects on HPDLSCs and PPDLSCs. An SMS of 12% induced optimal effects in HPDLSCs, including the highest proliferation, the best osteogenic ability, the lowest osteoclastogenesis, and the lowest secretion of inflammatory cytokines, while the optimal SMS for PPDLSCs was 8%. Excessive SMS damaged PPDLSCs function, including decreased proliferation, an imbalance between osteogenesis and osteoclastogenesis, and an activated inflammatory response. Our data suggest that PPDLSCs are more sensitive and less tolerant to SMS, and this may explain why mechanical force results in undesirable effects in periodontitis patients.


2014 ◽  
Vol 199 (5-6) ◽  
pp. 353-363 ◽  
Author(s):  
F.L. Wei ◽  
J.H. Wang ◽  
G. Ding ◽  
S.Y. Yang ◽  
Y. Li ◽  
...  

Author(s):  
Yiping Huang ◽  
Hao Liu ◽  
Runzhi Guo ◽  
Yineng Han ◽  
Yuhui Yang ◽  
...  

Orthodontic tooth movement is achieved by periodontal tissue remodeling triggered by mechanical force. It is essential to investigate the reaction of periodontal ligament stem cells (PDLSCs) for improving orthodontic therapeutic approaches. Autophagy is an endogenous defense mechanism to prevent mechanical damage of environmental change. Long non-coding RNAs (lncRNAs) are key regulators in gene regulation, but their roles are still largely uncharacterized in the reaction of PDLSCs during orthodontic tooth movement. In this study, we showed that autophagy was significantly induced in PDLSCs under compressive force, as revealed by the markers of autophagy, microtubule-associated protein light chain 3 (LC3) II/I and Beclin1, and the formation of autophagosomes. After the application of compressive force, lncRNA FER1L4 was strongly upregulated. Overexpression of FER1L4 increased the formation of autophagosome and autolysosomes in PDLSCs, while knockdown of FER1L4 reversed the autophagic activity induced by mechanical force. In mechanism, FER1L4 inhibited the phosphorylation of protein kinase B (AKT) and subsequently increased the nuclear translocation of forkhead box O3 (FOXO3) and thus mediated autophagic cascades under compressive strain. In mouse model, the expression of Lc3 as well as Fer1l4 was increased in the pressure side of periodontal ligament during tooth movement. These findings suggest a novel mechanism of autophagy regulation by lncRNA during periodontal tissue remodeling of orthodontic treatment.


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