MicroRNA-138 Inhibits Periodontal Progenitor Differentiation under Inflammatory Conditions

Zhou, Xiaofeng; Luan, Xianghong; Chen, Z.; Francis, Marybeth; Gopinathan, Gokul; Li, W.; Lu, Xuanyu; Li, S.; Wu, Christine D.; Diekwisch, Thomas G.H.

doi:10.1177/0022034515613043

Cited by 47 publications

(33 citation statements)

References 43 publications

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“…In the present study, miR-138 was responsible for the tissue damage and organ dysfunction induced by LPS. A previous study showed that miR-138 is increased due to inflammation situation in periodontitis model or in endothelial cells under stimulation with LPS [29,30], but miR-138 is only considered as a consequence of inflammation in these two studies. In the present study, we found that miR-138 not only increased as a result of inflammation but also acted as a regulator by targeting SIRT1, thus providing a potential target for sepsis treatment.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-138 Aggravates Inflammatory Responses of Macrophages by Targeting SIRT1 and Regulating the NF-κB and AKT Pathways

Bai

Zhang

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: With increased understanding of sepsis, mortality is decreasing. However, there is still a lack of effective therapeutic strategy. The inflammatory response of macrophages is critical during sepsis. Methods: Macrophages were stimulated with LPS. Western blotting and qRT-PCR were used to detect inflammatory responses. Then, the inhibitor of microRNA-138 was transfected and Western blotting, qRT-PCR, H&E staining and ELISA were used to verify the role of microRNA-138 in inflammation. Then target gene prediction databases were used to predict the potential target of microRNA-138. Both animal and cell models under LPS challenges were established to verify the regulation of SIRT1 and microRNA-138 during inflammation. Results: The present study showed that microRNA-138 was increased in macrophages stimulated with LPS. Additionally, the NF-κB and AKT pathways were both activated. The pre-treatment of microRNA-138 inhibitor decreased inflammatory factors, downregulated the NF-κB pathway, activated the AKT pathway and protected against organ damage in mice challenged with LPS. SIRT1 was demonstrated as a potential target of microRNA-138In macrophages stimulated with LPS, the inhibition effect of microRNA-138 inhibitor on inflammation was lost by SIRT1 siRNA pre-treatment. In the animal model, the protective effect of microRNA-138 antagomir disappeared in SIRT1 knockout mice. Conclusion: We demonstrated that miR-138 participated in the inflammatory process by inhibiting SIRT1 and activating the NF-κB pathway.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-138 Aggravates Inflammatory Responses of Macrophages by Targeting SIRT1 and Regulating the NF-κB and AKT Pathways

Bai

Zhang

Yang

et al. 2018

Cell Physiol Biochem

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“…Several studies have proved that miRNAs could be critical regulators in bone remodeling and inflammatory response such as periodontitis . The aberrant miRNA expression reacting to pathologic products, in turn, affects periodontitis . In our previous studies, it has been shown that microRNA‐335‐5p (miR‐335‐5p) could promote osteoblast differentiation and bone regeneration in vitro and in miR‐335‐5p transgenic (335‐Tg) mice via inhibiting DKK1, a Wnt pathway antagonist, which have been well‐characterized .…”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10] The aberrant miRNA expression reacting to pathologic products, in turn, affects periodontitis. [9][10][11] In our previous studies, it has been shown that microRNA-335-5p (miR-335-5p) could promote osteoblast differentiation and bone regeneration in vitro and in miR-335-5p transgenic (335-Tg) mice via inhibiting DKK1, a Wnt pathway antagonist, which have been well-characterized. [3][4][5] Besides, several studies have reported the inhibitive effects of miR-335-5p on bone-related disorders.…”

Section: Introductionmentioning

confidence: 99%

Potential roles of miR‐335‐5p on pathogenesis of experimental periodontitis

Lian

Liu

et al. 2019

J of Periodontal Research

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Background and Objective Periodontitis is a prevalent oral disease responsible for tooth loss. MicroRNAs have been proven crucial in bone disorders over the past decades. Promotive effect on osteogenic activities by microRNA‐335‐5p (miR‐335‐5p) has been well demonstrated, but its role involved in the pathogenesis of periodontitis remains elusive. In this study, we established experimental periodontitis (EP) on transgenic mice overexpressing miR‐335‐5p (335‐Tg) to investigate the novel effects of miR‐335‐5p on periodontal inflammation and bone loss. Methods Experimental periodontitis was established via ligation. The expression of inflammatory and osteoclastic genes was examined by quantitative real‐time PCR (qPCR). Morphology of alveolar bone was analyzed by microcomputed tomography (μCT). Hematoxylin and eosin (H&E), tartrate‐resistant acid phosphatase (TRAP), and Toll‐like receptor 4 (TLR4) immunohistochemistry (IHC) staining were conducted for histological analysis. Results The expression of miR‐335‐5p decreased significantly in the periodontal tissues of EP. Compared to the WT‐EP group, μCT analysis showed less bone loss in the 335‐Tg‐EP group accompanying with a decreased number of TRAP‐positive osteoclasts. H&E and IHC staining exhibited attenuated inflammation and TLR4 expression in the 335‐Tg‐EP group. Furthermore, reduced expressions of IL‐1β, IL‐6, TNF‐α, and TLR4 were also detected in the 335‐Tg‐EP group. Overexpression of miR‐335‐5p in vivo weakened the periodontal bone destruction and inflammation compared with the WT‐EP group. Conclusions Our data exhibit novel roles of miR‐335‐5p in preventing bone loss and inflammation in experimental periodontitis.

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“…Periodontitis is a set of chronic inflammatory disease of the periodontium, and aberrant miRNA expression may aggravate the disease progression (Xie et al, ). Previous studies have suggested that several miRNAs were abnormal expression in the progress of periodontal disease and regulated multifarious genes such as RUNX2, osteocalcin (OC), and EGFR (Motedayyen, Ghotloo, Saffari, Sattari, & Amid, ; Xie et al, ; Zhou et al, ). MiR‐218, a tumour suppressor, is significantly downregulated in various cancers (Deng et al, ; Shi et al, ) and inflammatory disorders (Xu et al, ).…”

Section: Discussionmentioning

confidence: 99%

Expression of Concern: MiRNA‐218 regulates osteoclast differentiation and inflammation response in periodontitis rats through Mmp9

Guo

Zeng

Miao

et al. 2019

Cellular Microbiology

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Periodontitis is a multiple infection and inflammatory disease featured by connective tissue homeostasis loss, periodontal inflammation, and alveolar bone resorption. MicroRNAs (miRNAs) are involved in the mediation of a large scale of pathological processes. Here, we show that miRNA‐218 provides protective effect on periodontitis via regulation of matrix metalloproteinase‐9 (Mmp9). This pathway is aberrant in periodontium from rats with periodontitis and human periodontal ligament progenitor cells stimulated by lipopolysaccharide, with downregulation of miR‐218 and higher levels of Mmp9 compared with periodontium from healthy rats and cells without stimulation. Overexpression of miR‐218 can suppress the degradation of Collagen Types I and IV and dentin sialoprotein (DSP), attenuate osteoclast formation, and inhibit the secretion of proinflammatory cytokines. On the other hand, overexpression of Mmp9 promotes the degradation of Collagen Types I and IV and DSP as well as RANKL‐induced osteoclast formation and elevates inflammatory factors levels. Furthermore, the inhibitory effect of miR‐218 was prevented by rescuing the Mmp9 expression. In addition, we also have showed that miR‐218 was able to attenuate bone resorption and inflammation in a periodontitis rat model. Collectively, our findings therefore suggest that miR‐218 acts as a protective role in periodontitis through the regulation of Mmp9.

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MicroRNA-138 Inhibits Periodontal Progenitor Differentiation under Inflammatory Conditions

Cited by 47 publications

References 43 publications

MicroRNA-138 Aggravates Inflammatory Responses of Macrophages by Targeting SIRT1 and Regulating the NF-κB and AKT Pathways

MicroRNA-138 Aggravates Inflammatory Responses of Macrophages by Targeting SIRT1 and Regulating the NF-κB and AKT Pathways

Potential roles of miR‐335‐5p on pathogenesis of experimental periodontitis

Expression of Concern: MiRNA‐218 regulates osteoclast differentiation and inflammation response in periodontitis rats through Mmp9

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