Knockdown of Yes-Associated Protein Induces the Apoptosis While Inhibits the Proliferation of Human Periodontal Ligament Stem Cells through Crosstalk between Erk and Bcl-2 Signaling Pathways

Yang, Wen; Ji, Yongming; Zhang, Yunpeng; Jiang, Baoqi; Tang, Cuizhu; Wang, Qi; Chen, Xiyan; Jia, Linglu; Gu, Wen; Xu, Xin

doi:10.7150/ijms.20504

Cited by 21 publications

(25 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Xu et al proved that YAP/TAZ was involved in the process of periodontal tissue remodeling during OTM in rat [ 25 ]. Furthermore, they demonstrated that knockdown of YAP induced the apoptosis and inhibited the proliferation of human periodontal ligament stem cells (h-PDLSCs) through crosstalk between Erk and Bcl-2 signaling pathway, suggesting that YAP signaling pathway participated in regulating biological behaviors of h-PDLSCs [ 26 ]. Diana Huelter-Hassler also found that the activated YAP might contribute to the enhanced proliferation of HPDLCs during orthodontic tooth movement [ 27 , 28 ].…”

Section: Resultsmentioning

confidence: 99%

Cyclic Stretch Enhances Osteogenic Differentiation of Human Periodontal Ligament Cells via YAP Activation

Yang

Wang

Chang

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

Periodontal remodeling and alveolar bone resorption and formation play essential roles during orthodontic tooth movement (OTM). In the process, human periodontal ligament cells (HPDLCs) sense and respond to orthodontic forces, contributing to the alveolar bone formation. However, the underlying mechanism in this process is not fully elucidated. In the present study, cyclic stress stimulus was applied on HPDLCs to mimic the orthodontic forces during OTM. Our results demonstrated that cyclic stretch promoted the osteogenic differentiation of HPDLCs. Moreover, our data suggested that yes-associated protein (YAP), the Hippo pathway effector, which also involved in mechanical signaling transduction, was activated as we found that the nuclear translocation of YAP was significantly increased in the cyclic stress treated HPDLCs. The mRNA expression of CTGF and CYR61, the target genes of YAP, was also remarkably increased. Furthermore, knockdown of YAP suppressed the cyclic stretch induced osteogenesis in HPDLCs, while overexpression of YAP in HPDLCs enhanced osteogenesis. We also noticed that YAP activities could be suppressed by the ROCK and nonmuscle myosin II inhibitors, Y-27632 and Blebbistatin. The inhibitors also significantly inhibited the cyclic stretch induced osteogenesis in HPDLCs. Finally, in the murine OTM model, our results revealed that YAP was upregulated and nuclearly translocated in the PDLCs at the tension side. In summary, our present study demonstrated that cytoskeleton remodeling induced activation of YAP signaling pathway was crucial for the cyclic stretch-induced osteogenesis of HPDLCs, which might play important roles during OTM.

show abstract

Section: Resultsmentioning

confidence: 99%

Cyclic Stretch Enhances Osteogenic Differentiation of Human Periodontal Ligament Cells via YAP Activation

Yang

Wang

Chang

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

show abstract

“… 16 - 18 . However, there are few studies on the expression of the Hippo/YAP pathway in human periodontal ligament stem cells (h-PDLSCs), and its exact function needs further exploration 19 - 21 . Therefore, the goal of the present study was to gain further insight into the expression and spatial distribution of YAP in h-PDLSCs, and to investigate the role of YAP in the regulation of proliferation, apoptosis, and senescence in h-PDLSCs.…”

Section: Introductionmentioning

confidence: 99%

Activated Yes-Associated Protein Accelerates Cell Cycle, Inhibits Apoptosis, and Delays Senescence in Human Periodontal Ligament Stem Cells

Jia¹,

Gu²,

Zhang³

et al. 2018

Int. J. Med. Sci.

Self Cite

View full text Add to dashboard Cite

Objectives: To provide insight into the biological effects of activated Yes-associated protein (YAP) on the proliferation, apoptosis, and senescence of human periodontal ligament stem cells (h-PDLSCs).Methods: h-PDLSCs were isolated by the limiting dilution method, and their surface markers were quantified by flow cytometry. Enhanced green fluorescence protein (EGFP)-labeled lentiviral vector was used to activate YAP in h-PDLSCs, then qRT-PCR and Western blotting were used to evaluate the expression level of YAP. Immunofluorescence was used to detect the location of YAP in h-PDLSCs. The proliferation activity was detected by cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU), and the cell cycle was determined by flow cytometry. Apoptosis was analyzed by Annexin V-APC staining. Cell senescence was detected by β-galactosidase staining. Proteins in ERK, Bcl-2, and p53 signaling pathways were detected by Western blotting.Results: h-PDLSCs were isolated successfully and were positive for human mesenchymal stem cell surface markers. After YAP was activated by lentiviral vector, the mRNA and protein of YAP were highly expressed, and more YAP translocated into the nucleus. When YAP was overexpressed in h-PDLSCs, proliferation activity was improved; early and late apoptosis rates decreased (P<0.05); the proportion of cells in G2/M phases increased (P<0.05), while that in G0/G1 phase decreased (P<0.05); cellular senescence was delayed (P<0.01); the expression of P-MEK, P-ERK, P-P90RSK and P-Msk increased, while the expression of Bcl-2 family members (Bak, Bid and Bik) decreased.Conclusions: Activated YAP promotes proliferation, inhibits apoptosis, and delays senescence of h-PDLSCs. The Hippo-YAP signaling pathway can influence ERK and Bcl-2 signaling pathways.

show abstract

“…Previous reports have also indicated that Yap is precisely governed by the ERK pathway [ 40 ]. We conducted western blotting assays of p-ERK and Yap to determine their relationship.…”

Section: Resultsmentioning

confidence: 99%

Mitochonic acid 5 activates the MAPK–ERK–yap signaling pathways to protect mouse microglial BV-2 cells against TNFα-induced apoptosis via increased Bnip3-related mitophagy

Lei

Tan

et al. 2018

Cell Mol Biol Lett

View full text Add to dashboard Cite

BackgroundThe regulation of microglial function via mitochondrial homeostasis is important in the development of neuroinflammation. The underlying mechanism for this regulatory function remains unclear. In this study, we investigated the protective role of mitochonic acid 5 (MA-5) in microglial mitochondrial apoptosis following TNFα-induced inflammatory injury.MethodsTNFα was used to induce inflammatory injury in mouse microglial BV-2 cells with and without prior MA-5 treatment. Cellular apoptosis was assessed using the MTT and TUNEL assays. Mitochondrial functions were evaluated via mitochondrial membrane potential JC-1 staining, ROS flow cytometry analysis, mPTP opening assessment, and immunofluorescence of cyt-c. Mitophagy was examined using western blots and immunofluorescence. The pathways analysis was carried out using western blots and immunofluorescence with a pathway blocker.ResultsOur results demonstrated that TNFα induced apoptosis in the microglial BV-2 cell line by activating the caspase-9-dependent mitochondrial apoptotic pathway. Mechanistically, inflammation reduced mitochondrial potential, induced ROS production, and contributed to the leakage of mitochondrial pro-apoptotic factors into the cytoplasm. The inflammatory response reduced cellular energy metabolism and increased oxidative stress. By contrast, treatment with MA-5 reduced mitochondrial apoptosis via upregulation of mitophagy. Increased mitophagy degraded damaged mitochondria, disrupting mitochondrial apoptosis, neutralizing ROS overproduction, and improving cellular energy production. We also identified that MA-5 regulated mitophagy via Bnip3 through the MAPK–ERK–Yap signaling pathway. Inhibiting this signaling pathway or knocking down Bnip3 expression prevented MA-5 from having beneficial effects on mitochondrial homeostasis and increased microglial apoptosis.ConclusionsAfter TNFα-induced inflammatory injury, MA-5 affects microglial mitochondrial homeostasis in a manner mediated via the amplification of protective, Bnip3-related mitophagy, which is mediated via the MAPK–ERK–Yap signaling pathway.

show abstract

Knockdown of Yes-Associated Protein Induces the Apoptosis While Inhibits the Proliferation of Human Periodontal Ligament Stem Cells through Crosstalk between Erk and Bcl-2 Signaling Pathways

Cited by 21 publications

References 34 publications

Cyclic Stretch Enhances Osteogenic Differentiation of Human Periodontal Ligament Cells via YAP Activation

Cyclic Stretch Enhances Osteogenic Differentiation of Human Periodontal Ligament Cells via YAP Activation

Activated Yes-Associated Protein Accelerates Cell Cycle, Inhibits Apoptosis, and Delays Senescence in Human Periodontal Ligament Stem Cells

Mitochonic acid 5 activates the MAPK–ERK–yap signaling pathways to protect mouse microglial BV-2 cells against TNFα-induced apoptosis via increased Bnip3-related mitophagy

Contact Info

Product

Resources

About