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P38 MAPK signaling is a key mediator for low-intensity pulsed ultrasound (LIPUS) in cultured human omental adipose-derived mesenchymal stem cells.

ABSTRACT: Visceral obesity is an independent risk factor for cardiovascular disorders and lacks effective, non-drug based clinical therapy. The use of low-intensity pulsed ultrasound (LIPUS) to treat chronic pain and bone fracture is well-known, but its application for visceral obesity treatment has not been studied. Here, we evaluated the therapeutic potential of LIPUS by studying its effects, at varying doses, on human omental adipose-derived mesenchymal stem cells (hAMSCs). LIPUS stimulation was applied for 1 min at intensities between 70 and 210 mW/cm2. Cell viability was measured using the Cell Counting Kit-8 assay. Cell apoptosis was quantified by flow cytometry and immunoblotting of apoptosis marker proteins. We found that a high dose of LIPUS (210 mW/cm2) promoted apoptosis in hAMSCs, while a low dose (70 mW/cm2) increased hAMSC viability. Phosphorylation of p38, a mitogen-activated protein kinase (MAPK), increased with high dose LIPUS treatment, but markedly decreased with a low dose. Inhibition of p38 phosphorylation by SB203580, an inhibitor of p38 MAPK activity, rescued the apoptotic effects of high dose LIPUS. Our results showed the dose-dependent, opposing effects of LIPUS on hAMSCs and suggested that p38 plays a key role in mediating the effects of LIPUS on hAMSCs.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6357340 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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p38 MAPK signaling is a key mediator for low-intensity pulsed ultrasound (LIPUS) in cultured human omental adipose-derived mesenchymal stem cells.

Wang Yaqing Y Jiang Li L Xu Tianhua T Su Zhongping Z Guo Xiasheng X Tu Juan J Zhang Dong D Sun Wei W Kong Xiangqing X

American journal of translational research 20190115 1

Visceral obesity is an independent risk factor for cardiovascular disorders and lacks effective, non-drug based clinical therapy. The use of low-intensity pulsed ultrasound (LIPUS) to treat chronic pain and bone fracture is well-known, but its application for visceral obesity treatment has not been studied. Here, we evaluated the therapeutic potential of LIPUS by studying its effects, at varying doses, on human omental adipose-derived mesenchymal stem cells (hAMSCs). LIPUS stimulation was applie ...[more]

PMID: 30787998

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Project description:BackgroundBone marrow-derived mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs) have shown potent anti-inflammatory function in various pathological conditions, such as osteoarthritis and neurodegenerative diseases. Since the number of EVs naturally secreted by cells is finite and they usually bear specific repertoires of bioactive molecules to perform manifold cell-cell communication, but not one particular therapeutic function as expected, their practical application is still limited. Strategies are needed to increase the production of EVs and enhance their therapeutic function. Recent studies have suggested that low-intensity pulsed ultrasound (LIPUS) is a promising non-invasive method to increase the secretion of EVs and promote their anti-inflammatory effects. However, the effect of LIPUS stimulation of BMSCs on EVs derived from the cells remains unclear. The objective of this study was to investigate whether LIPUS stimulation on BMSCs could increase the secretion of EVs and enhance their anti-inflammatory effects.MethodsBMSCs were exposed to LIPUS (300 mW/cm2) for 15 min and EVs were isolated by ultracentrifugation. Anti-inflammatory effects of EVs were investigated on RAW264.7 cells in vitro and in the allogeneic skin transplantation model. Small RNA-seq was utilized to identify components difference in EVs with/without LIPUS irradiation.ResultsIn this study, we found that LIPUS stimulation could lead to a 3.66-fold increase in the EVs release from BMSCs. Moreover, both in vitro and in vivo experimental results suggested that EVs secreted from LIPUS-treated BMSCs (LIPUS-EVs) possessed stronger anti-inflammatory function than EVs secreted from BMSCs without LIPUS stimulation (C-EVs). RNA-seq analysis revealed that miR-328-5p and miR-487b-3p were significantly up-regulated in LIPUS-EVs compare with C-EVs. The suppression of MAPK signaling pathway by these two up-regulated miRNAs could be the potential mechanism of strengthened anti-inflammatory effects of LIPUS-EVs.ConclusionLIPUS stimulation on BMSCs could significantly increase the secretion of EVs. Moreover, EVs generated from LIPUS-treated BMSCs possessed much stronger anti-inflammatory function than C-EVs. Therefore, LIPUS could be a promising non-invasive strategy to promote the production of EVs from BMSCs and augment their anti-inflammatory effects.

Project description:BackgroundHuman amnion-derived mesenchymal stem cells (hAD-MSCs) have the features of mesenchymal stem cells (MSCs). Low-intensity pulsed ultrasound (LIPUS) can promote the expression of various growth factors and anti-inflammatory molecules that are necessary to keep the follicle growing and to reduce granulosa cell (GC) apoptosis in the ovary. This study aims to explore the effects of LIPUS-pretreated hAD-MSC transplantation on chemotherapy-induced primary ovarian insufficiency (POI) in rats.MethodsThe animals were divided into control, POI, hAD-MSC treatment, and LIPUS-pretreated hAD-MSC treatment groups. POI rat models were established by intraperitoneal injection of cyclophosphamide (CTX). The hAD-MSCs isolated from the amnion were exposed to LIPUS or sham irradiation for 5 consecutive days and injected into the tail vein of POI rats. Expression and secretion of growth factors promoted by LIPUS in hAD-MSCs were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) in vitro. Estrous cycle, serum sex hormone levels, follicle counts, ovarian pathological changes, GC apoptosis, Bcl2 and Bax expression, and pro-inflammatory cytokine levels in ovaries were examined.ResultsPrimary hAD-MSCs were successfully isolated from the amnion. LIPUS promoted the expression and secretion of growth factors in hAD-MSCs in vitro. Both hAD-MSC and LIPUS-pretreated hAD-MSC transplantation increased the body and reproductive organ weights, improved ovarian function, and reduced reproductive organ injuries in POI rats. Transplantation of hAD-MSCs increased the Bcl-2/Bax ratio and reduced GC apoptosis and ovarian inflammation induced by chemotherapy in ovaries. These effects could be improved by pretreatment with LIPUS on hAD-MSCs.ConclusionBoth hAD-MSC transplantation and LIPUS-pretreated hAD-MSC transplantation can repair ovarian injury and improve ovarian function in rats with chemotherapy-induced POI. LIPUS-pretreated hAD-MSC transplantation is more advantageous for reducing inflammation, improving the local microenvironment, and inhibiting GC apoptosis induced by chemotherapy in ovarian tissue of POI rats.

Project description:BackgroundNon-union occurs in approximately 5 to 10% of fracture patients, with certain bones at greater risk of failing to heal. Non-unions have a significant impact on socioeconomic costs and the patients short and long-term quality of life. Low intensity pulsed ultrasound (LIPUS) is a non-invasive therapy for non-union treatment that can improve the long-term outcome. The purpose of this study is to summarize the available literature assessing LIPUS potential to improve the union rate in instrumented, infected, and fragility non-unions.MethodsA literature search was conducted in the MEDLINE, EMBASE, and CINAHL databases for all relevant literature on the healing rates of LIPUS utilized in instrumented, infected, and fragility non-unions. Study characteristics were summarized for each of the included studies. The percentage of healed patients (healing rate), for instrumented, infected, and fragility fracture non-union patients were pooled from each included study.ResultsThe literature search identified a total of 326 articles, while searching reference lists and grey literature identified an additional 3 articles. There was a total of 29 articles included in this review, with 20 articles included within the quantitative synthesis of healing rates. The most common design of included studies was case series (17 articles), followed by case reports (9 articles). Studies were primarily retrospective (18 studies), with an additional 10 prospective studies. Non-union healing rates were 82% (95% CI: 76 to 87%) in instrumented, 82% (95% CI: 70 to 95%) in infected, and 91% (95% CI: 87 to 95%) in fragility fracture patients with non-unions.ConclusionThis study has provided a thorough overview of the current literature on LIPUS treatment for instrumented, infected, and fragility fracture non-unions. The healing rates for non-unions in these subgroups were comparable to healing rates observed with LIPUS use in general non-union literature. LIPUS treatment should be considered as a conservative non-surgical treatment option to potentially reduce the socioeconomic impact and improve the quality of life of these unfortunate patients.Level of evidence4 (systematic review of primarily case series data).

Dataset Information

P38 MAPK signaling is a key mediator for low-intensity pulsed ultrasound (LIPUS) in cultured human omental adipose-derived mesenchymal stem cells.

Publications

p38 MAPK signaling is a key mediator for low-intensity pulsed ultrasound (LIPUS) in cultured human omental adipose-derived mesenchymal stem cells.

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