Irisin promotes cementoblast differentiation via p38 MAPK pathway

Zhu, Jiaqi; Wang, Yunlong; Cao, Zhengguo; Du, Mingyuan; Hao, Yunru; Pan, Jiawen; He, Hong

doi:10.1111/odi.13307

Cited by 17 publications

(13 citation statements)

References 36 publications

(61 reference statements)

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“…Studies showed that FNDC5/Irisin is expressed in adipose tissue, cardiomyocytes, the brain and other parts of the body [ 12 , 13 ]. Recently the interest in the molecular actions of Irisin revealed that it is not only involved in energy storage and sensing, but it has a variety of molecular functions including differentiation, inflammation, oxidative stress in different systems [ 14 , 15 , 16 , 17 , 18 ]. The inhibitory effects of Irisin on cell apoptosis was shown to occur by modulation of pro-apoptotic markers such as the BCL2 associated agonist of death (BAD), BCL2 associated X apoptosis regulator (BAX), Caspase-9 and Caspase-3 and anti-apoptotic proteins such as BCL-2 and BCL-XL [ 16 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Irisin Protects the Human Placenta from Oxidative Stress and Apoptosis via Activation of the Akt Signaling Pathway

Kohan-Ghadr¹,

Armistead²,

Berg³

et al. 2021

IJMS

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Irisin is a newly discovered exercise-mediated polypeptide hormone. Irisin levels increase during pregnancy however, women with preeclampsia (PE) have significantly lower levels of Irisin compared to women of healthy pregnancies. Even though many studies suggest a role of Irisin in pregnancy, its function in the human placenta is unclear. In the current study, we aimed to understand key roles of Irisin through its ability to protect against apoptosis is the preeclamptic placenta and in ex vivo and in vitro models of hypoxia/re-oxygenation (H/R) injury. Our studies show that Irisin prevents cell death by reducing pro-apoptotic signaling cascades, reducing cleavage of PARP to induce DNA repair pathways and reducing activity of Caspase 3. Irisin caused an increase in the levels of anti-apoptotic BCL2 to pro-apoptotic BAX and reduced ROS levels in an in vitro model of placental ischemia. Furthermore, we show that Irisin treatment acts through the Akt signaling pathway to prevent apoptosis and enhance cell survival. Our findings provide a novel understanding for the anti-apoptotic and pro-survival properties of Irisin in the human placenta under pathological conditions. This work yields new insights into placental development and disease and points towards intervention strategies for placental insufficiencies, such as PE, by protecting and maintaining placental function through inhibiting hypoxic ischemia-induced apoptosis.

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Section: Introductionmentioning

confidence: 99%

Irisin Protects the Human Placenta from Oxidative Stress and Apoptosis via Activation of the Akt Signaling Pathway

Kohan-Ghadr¹,

Armistead²,

Berg³

et al. 2021

IJMS

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“…In our previous studies, irisin promoted cementoblast differentiation via the p38 MAPK pathway 4 . Our laboratory previously discovered that miRNA‐3064‐3p mediates cementoblast differentiation by targeting DKK1 5 .…”

Section: Introductionmentioning

confidence: 94%

“…In our previous studies, irisin promoted cementoblast differentiation via the p38 MAPK pathway. 4 Our laboratory previously discovered that miRNA-3064-3p mediates cementoblast differentiation by targeting DKK1. 5 These results suggest that cementoblast differentiation is controlled on both transcriptional and post-transcriptional levels.…”

Section: Introductionmentioning

confidence: 99%

CircRNA Lrp6 promotes cementoblast differentiation via miR‐145a‐5p/Zeb2 axis

Wang

et al. 2021

J of Periodontal Research

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Background and Objective: Cementum is a part of the periodontium and anchors periodontal ligaments to the alveolar bone. Cementoblasts are responsible for the cementum formation via matrix deposition and subsequently mineralization. Thus, exploring novel mechanisms underlying the function of cementoblast contributes to the treatment of cementum damage. Recently, circRNA Lrp6 (circLRP6) has been of interest due to its active role in cell differentiation, but its potential role in cementoblast differentiation remains unclear. Herein, we attempted to elucidate the role of circLRP6 in cementoblast differentiation and clarify any associated mechanisms. Material and Methods:The mRNA expressions of circLRP6, miR-145a-5p, zinc finger E-box binding homeobox 2 (Zeb2), runt-related transcription factor 2 (Runx2), osteopontin (Opn), and bone sialoprotein (Bsp) were evaluated by qRT-PCR. The protein levels of Zeb2 were measured by Western blot. Bioinformatic analysis and dual-luciferase reporter assays were used to test the potential binding targets of miR-145a-5p. The differentiation potentials of the cementoblasts were assessed by Alkaline phosphatase (ALP) staining, ALP activity assay, Alizarin red S (ARS) staining, and quantification.Results: In this study, circLRP6 was significantly upregulated in cementoblast differentiation. Furthermore, circLRP6 knockdown inhibited ALP levels, reduced calcium nodule formation and the expression of Runx2, Opn, and Bsp. Mechanically, bioinformatic analysis and dual-luciferase reporter assays confirmed miR-145a-5p was a potential binding target of circLRP6. miR-145a-5p can negatively regulate cementoblast differentiation. Subsequently, bioinformatic analysis and dual-luciferase reporter assays confirmed Zeb2 was a potential miR-145a-5p target. miR-145a-5p overexpression resulted in a downregulation of Zeb2. Furthermore, Zeb2 inhibition partially reversed the effect of circLRP6 during cementoblast differentiation. Conclusion:Taken together, circLRP6 appears to modulate cementoblast differentiation by antagonizing the function of miR-145a-5p, thereby increasing Zeb2. This study serves as a stepping stone for the potential development of an approach to promote cementum formation.

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“…[17][18][19] Our group previously proved that cementoblasts express PGC-1α. 20 However, the role of PGC-1α in cementoblasts under inflammatory environment is totally unknown.…”

Section: Introductionmentioning

confidence: 99%

PGC‐1α attenuates TNF‐α‐induced inflammatory responses in OCCM‐30 cells

Cao

et al. 2022

J of Periodontal Research

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Background and Objectives Peroxisome proliferator‐activated receptor‐γ coactivator (PGC)‐1α, a master regulator of mitochondrial biogenesis and oxidative metabolism, has been associated with many inflammatory diseases. However, little is known about the function and mechanism of PGC‐1α in cementoblasts under periodontitis. Our study aimed to investigate the effects of PGC‐1α in immortalized cementoblast cell line OCCM‐30 under TNF‐α stimulation. Materials and Methods OCCM‐30 cells were cultured and exposed to TNF‐α, and PGC‐1α expression was assessed by Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting. Chemical inhibitors targeting various signaling pathways including NF‐κB, p38 MAPK, Akt, and p53 were used to identify the regulatory mechanism involved. ZLN005 was used to upregulate PGC‐1α and the subsequent alteration of inflammatory cytokines expression under TNF‐α stimulation were examined by qRT‐PCR and Elisa. PGC‐1α siRNA was employed to further verify the role of PGC‐1α in inflammatory response. Dual‐reporter gene assays were performed to examine the transcriptional activity of p65, and the phosphorylation level of p65 was evaluated by western blotting. Immunofluorescence assays and nuclear and cytoplasmic extractions were performed to check the nuclear translocation of p65. Coimmunoprecipitation studies were also performed to check whether there is direct binding between p65 and PGC‐1α. Results TNF‐α suppressed PGC‐1α expression in OCCM‐30 cells. Blocking p38 MAPK pathways restored the expression of PGC‐1α. ZLN005 can upregulate PGC‐1α in OCCM‐30 cells. The upregulation of PGC‐1α by ZLN005 inhibited TNF‐α‐induced proinflammatory cytokine expression, which was impaired by the transfection of PGC‐1α siRNA. Knocking down PGC‐1α also partially restored the ZLN005‐decreased transcriptional activity of p65. However, the phosphorylation level and nuclear translocation of p65 were not significantly affected by PGC‐1α. It was found that p65 was bound to PGC‐1α in OCCM‐30 cells stimulated by TNF‐α, and the binding was increased upon ZLN005 treatment. Conclusions PGC‐1α can attenuate TNF‐α‐induced inflammatory responses in OCCM‐30 cells.

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Irisin promotes cementoblast differentiation via p38 MAPK pathway

Cited by 17 publications

References 36 publications

Irisin Protects the Human Placenta from Oxidative Stress and Apoptosis via Activation of the Akt Signaling Pathway

Irisin Protects the Human Placenta from Oxidative Stress and Apoptosis via Activation of the Akt Signaling Pathway

CircRNA Lrp6 promotes cementoblast differentiation via miR‐145a‐5p/Zeb2 axis

PGC‐1α attenuates TNF‐α‐induced inflammatory responses in OCCM‐30 cells

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