Small Extracellular Vesicles Released from Bioglass/Hydrogel Scaffold Promote Vascularized Bone Regeneration by Transferring miR-23a-3p

Abstract Background The treatment of critical-size bone defect is a great difficulty in orthopedics. Osteogenesis and angiogenesis are critical issue during the process of bone repair and remodeling. MSCs-derived small extracellular vesicles (sEVs) show desirable therapeutic prospects in tissue regeneration due to satisfied advantages including high stability, facilitated acquisition and abundant source. However, the effect of Human umbilical cord MSCs-derived sEVs (hUC-MSCs-sEVs) on vascularized bone regeneration and the potential mechanism remains to be investigated. Herein, we aimed to explore the therapeutic effect and the mechanism of hUC-MSCs-sEVs on critical-size bone defect. Methods To investigate the potential osteogenesis and angiogenesis effects of sEVs in vitro, we extracted sEVs from hUC-MSCs, and then sEVs were co-incubated with BMSCs and HUVECs. We next investigated the potential mechanism of sEVs on the effects of osteogenesis and angiogenesis by luciferase reporter gene assay and western blot. We fabricated 3D-printed bioglass scaffold with Gelma/nanoclay hydrogel coatings to load sEVs(BG-gel-sEVs) to ensure in vivo sustained efficacy of sEVs. Finally, the skull defect model was used to evaluate the capacity of vascularized bone regeneration of the composited scaffolds. Results hUC-MSCs-sEVs facilitated calcium deposition and the endothelial network formation, inducing osteogenic differentiation and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway. Additionally, the BG-gel-sEVs composited scaffold achieved vascularized bone regeneration in vivo. Conclusion This finds illuminated that hUC-MSCs-sEVs promoted osteogenesis and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway, achieving vascularized bone regeneration.

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IL-8 Enhances Therapeutic Effects of BMSCs on Bone Regeneration via CXCR2-Mediated PI3k/Akt Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000491742 ◽

2018 ◽

Vol 48 (1) ◽

pp. 361-370 ◽

Cited By ~ 15

Author(s):

Aijun Yang ◽

Yanzhu Lu ◽

Junchao Xing ◽

Zhilin Li ◽

Xiaolong Yin ◽

...

Keyword(s):

Bone Regeneration ◽

Signaling Pathway ◽

Bone Defect ◽

Chondrogenic Differentiation ◽

Akt Signaling ◽

Host Cells ◽

Therapeutic Effects ◽

Akt Signaling Pathway

Background/Aims: Tissue engineering bone transplantation with bone marrow mesenchymal stem cells (BMSCs) is an effective technology to treat massive bone loss, while molecular regulation of the bone regeneration processes remains poorly understood. Here, we aimed to assess the role of interleukin-8 (IL-8) in the recruitment of host cells by seeded BMSCs and in the bone regeneration. Methods: A transwell assay was performed to examine the role of IL-8/CXCR1/CXCR2/PI3k/Akt on the migration potential of hBMSCs. The in vitro chondrogenic differentiation of hBMSCs was assessed by examination of 2 chondrogenic markers, Sox9 and type 2 collagen (COL2). mBMSCs were used in tissue engineered bone (TEB) with/without IL-8 implanted into bone defect area with CXCR2 or Akt inhibitors. Density and Masson staining of the regenerated bone were assessed. The chondrogenesis was assessed by expression levels of associated proteins, Sox9 and COL2, by RT-qPCR and by immunohistochemistry. Results: IL-8 may trigger in vitro migration of hBMSCs via CXCR2-mediated PI3k/Akt signaling pathway. IL-8 enhances osteogenesis in the TEB-implanted bone defect in mice. IL-8 induces chondrogenic differentiation of hBMSCs via CXCR2-mediated PI3k/Akt signaling pathway in vitro and in vivo. Conclusions: IL-8 enhances therapeutic effects of MSCs on bone regeneration via CXCR2-mediated PI3k/Akt signaling pathway.

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In vivo cooperation between Bcl‐x L and the phosphoinositide 3‐kinase‐Akt signaling pathway for the protection of epidermal keratinocytes from apoptosis

The FASEB Journal ◽

10.1096/fj.02-0597com ◽

2003 ◽

Vol 17 (6) ◽

pp. 610-620 ◽

Cited By ~ 37

Author(s):

Jiro Umeda ◽

Shigetoshi Sano ◽

Kazuhiko Kogawa ◽

Noboru Motoyama ◽

Kunihiko Yoshikawa ◽

...

Keyword(s):

Signaling Pathway ◽

Akt Signaling ◽

Epidermal Keratinocytes ◽

Akt Signaling Pathway ◽

Phosphoinositide 3 Kinase

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Silencing of lncRNA UCA1 inhibited the pathological progression in PCOS mice through the regulation of PI3K/AKT signaling pathway

Journal of Ovarian Research ◽

10.1186/s13048-021-00792-2 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Dongyong Yang ◽

Yanqing Wang ◽

Yajing Zheng ◽

Fangfang Dai ◽

Shiyi Liu ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Signaling Pathway ◽

Structural Damage ◽

Polycystic Ovary ◽

Serum Insulin ◽

Tumor Cell Line ◽

Akt Signaling ◽

Akt Signaling Pathway

Abstract Background Polycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-aged women worldwide, however, the mechanisms and progression of PCOS still unclear due to its heterogeneous nature. Using the human granulosa-like tumor cell line (KGN) and PCOS mice model, we explored the function of lncRNA UCA1 in the pathological progression of PCOS. Results CCK8 assay and Flow cytometry were used to do the cell cycle, apoptosis and proliferation analysis, the results showed that UCA1 knockdown in KGN cells inhibited cell proliferation by blocking cell cycle progression and promoted cell apoptosis. In the in vivo experiment, the ovary of PCOS mice was injected with lentivirus carrying sh-UCA1, the results showed that knockdown of lncRNA UCA1 attenuated the ovary structural damage, increased the number of granular cells, inhibited serum insulin and testosterone release, and reduced the pro-inflammatory cytokine production. Western blot also revealed that UCA1 knockdown in PCOS mice repressed AKT activation, inhibitor experiment demonstrated that suppression of AKT signaling pathway, inhibited the cell proliferation and promoted apoptosis. Conclusions Our study revealed that, in vitro, UCA1 knockdown influenced the apoptosis and proliferation of KGN cells, in vivo, silencing of UCA1 regulated the ovary structural damage, serum insulin release, pro-inflammatory production, and AKT signaling pathway activation, suggesting lncRNA UCA1 plays an important role in the pathological progression of PCOS.

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Squamosamide derivative FLZ protected dopaminergic neuron by activating Akt signaling pathway in 6-OHDA-induced in vivo and in vitro Parkinson's disease models

Brain Research ◽

10.1016/j.brainres.2013.12.026 ◽

2014 ◽

Vol 1547 ◽

pp. 49-57 ◽

Cited By ~ 17

Author(s):

Xiu-Qi Bao ◽

Xiang-Chen Kong ◽

Li-Bing Kong ◽

Liang-Yu Wu ◽

Hua Sun ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Signaling Pathway ◽

Dopaminergic Neuron ◽

Akt Signaling ◽

Disease Models ◽

Akt Signaling Pathway

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A77 1726 (leflunomide) blocks and reverses cardiac hypertrophy and fibrosis in mice

Clinical Science ◽

10.1042/cs20180160 ◽

2018 ◽

Vol 132 (6) ◽

pp. 685-699 ◽

Cited By ~ 20

Author(s):

Zhen-Guo Ma ◽

Xin Zhang ◽

Yu-Pei Yuan ◽

Ya-Ge Jin ◽

Ning Li ◽

...

Keyword(s):

T Cell ◽

Cardiac Hypertrophy ◽

Protective Effect ◽

Signaling Pathway ◽

Cardiac Fibrosis ◽

Pressure Overload ◽

Akt Signaling ◽

Akt Signaling Pathway

T-cell infiltration and the subsequent increased intracardial chronic inflammation play crucial roles in the development of cardiac hypertrophy and heart failure (HF). A77 1726, the active metabolite of leflunomide, has been reported to have powerful anti-inflammatory and T cell-inhibiting properties. However, the effect of A77 1726 on cardiac hypertrophy remains completely unknown. Herein, we found that A77 1726 treatment attenuated pressure overload or angiotensin II (Ang II)-induced cardiac hypertrophy in vivo, as well as agonist-induced hypertrophic response of cardiomyocytes in vitro. In addition, we showed that A77 1726 administration prevented induction of cardiac fibrosis by inhibiting cardiac fibroblast (CF) transformation into myofibroblast. Surprisingly, we found that the protective effect of A77 1726 was not dependent on its T lymphocyte-inhibiting property. A77 1726 suppressed the activation of protein kinase B (AKT) signaling pathway, and overexpression of constitutively active AKT completely abolished A77 1726-mediated cardioprotective effects in vivo and in vitro. Pretreatment with siRNA targetting Fyn (si Fyn) blunted the protective effect elicited by A77 1726 in vitro. More importantly, A77 1726 was capable of blocking pre-established cardiac hypertrophy in mice. In conclusion, A77 1726 attenuated cardiac hypertrophy and cardiac fibrosis via inhibiting FYN/AKT signaling pathway.

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Cyanidin inhibits EMT induced by oxaliplatinviatargeting the PDK1–PI3K/Akt signaling pathway

Food & Function ◽

10.1039/c8fo01611a ◽

2019 ◽

Vol 10 (2) ◽

pp. 592-601 ◽

Cited By ~ 6

Author(s):

Xiang Li ◽

Ze-sheng Zhang ◽

Xiao-han Zhang ◽

Sheng-nan Yang ◽

Dong Liu ◽

...

Keyword(s):

Antitumor Activity ◽

Signaling Pathway ◽

Akt Signaling ◽

Akt Signaling Pathway

Anthocyanins have been shown to exhibit antitumor activity in several cancersin vitroandin vivo.

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In vitro and in vivo Induction of p53-Dependent Apoptosis by Extract of Euryale ferox Salisb in A549 Human Caucasian Lung Carcinoma Cancer Cells Is Mediated Through Akt Signaling Pathway

Frontiers in Oncology ◽

10.3389/fonc.2019.00406 ◽

2019 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Gun-He Nam ◽

Kyung-Jo Jo ◽

Ye-Seul Park ◽

Hye Won Kawk ◽

Sang-Yong Kim ◽

...

Keyword(s):

Cancer Cells ◽

Signaling Pathway ◽

Lung Carcinoma ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Euryale Ferox ◽

In Vivo Induction

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Luteolin Exerts Cardioprotective Effects through Improving Sarcoplasmic Reticulum Ca2+-ATPase Activity in Rats during Ischemia/Reperfusion In Vivo

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/365854 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 9

Author(s):

Changsheng Nai ◽

Haochen Xuan ◽

Yingying Zhang ◽

Mengxiao Shen ◽

Tongda Xu ◽

...

Keyword(s):

Sarcoplasmic Reticulum ◽

Signaling Pathway ◽

Myocardial Infarct ◽

Ischemia Reperfusion ◽

Akt Signaling ◽

Myocardial Infarct Size ◽

Akt Signaling Pathway ◽

Cardioprotective Effects

The flavonoid luteolin exists in many types of fruits, vegetables, and medicinal herbs. Our previous studies have demonstrated that luteolin reduced ischemia/reperfusion (I/R) injury in vitro, which was related with sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity. However, the effects of luteolin on SERCA2a activity during I/R in vivo remain unclear. To investigate whether luteolin exerts cardioprotective effects and to monitor changes in SERCA2a expression and activity levels in vivo during I/R, we created a myocardial I/R rat model by ligating the coronary artery. We demonstrated that luteolin could reduce the myocardial infarct size, lactate dehydrogenase release, and apoptosis during I/R injury in vivo. Furthermore, we found that luteolin inhibited the I/R-induced decrease in SERCA2a activity in vivo. However, neither I/R nor luteolin altered SERCA2a expression levels in myocardiocytes. Moreover, the PI3K/Akt signaling pathway played a vital role in this mechanism. In conclusion, the present study has confirmed for the first time that luteolin yields cardioprotective effects against I/R injury by inhibiting the I/R-induced decrease in SERCA2a activity partially via the PI3K/Akt signaling pathway in vivo, independent of SERCA2a protein level regulation. SERCA2a activity presents a novel biomarker to assess the progress of I/R injury in experimental research and clinical applications.

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