Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells

BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process.

Effects of low-intensity pulsed ultrasound stimulation on porous hydroxyapatite blocks for posterolateral fusion of lumbar spine in rabbits

he effects of porous hydroxyapatite blocks（PHABs） and an adjunct low-intensity pulsed ultrasound stimulation（LIPUS） on the fusion rate in a rabbit spinal posterolateral fusion（PLF） model were evaluated.Twenty rabbits underwent PLF with autograft and PHABs were randomly assigned to two groups：treated group with 20 min LIPUS daily and untreated control group for 4 weeks until euthanasia.The fused motion segments were subjected to manual palpation,gross observation,and radiographic investigation before histomorphologic and scanning electron microscopic analyses.Statistical differences between the LIPUS group and the control group are found in the fusion rate,bone density gray scale,trabecular bone formation,osteoblast-like cells,chondrocytes and positive expression of BMP-2 and TGF-β1 in the junction zone（significance level p〈0.05）.The results suggest that LIPUS can increase fusion rates and accelerate bone in-growth into PHAB.Hence,PHAB and LIPUS may be used together to increase fusion rates in a rabbit spinal fusion model with a promising extension to human application.

Effect of low-intensity pulsed ultrasound on posterolateral lumbar fusion of rabbit

Objective:To observe the effect of low-intensity pulsed ultrasound in the posterolateral Lumbar fusion of rabbit.Methods:A total of 48 New Zealand white rabbits were randomly divided into the observation group and control group,including the autogenous iliac observation group.artificial bone observation group,artificial bone control group and autogenous iliac control group according to the different bone grafting.The posterolateral lumbar fusion of rabbits in each group was analyzed and compared.Results:After 4 weeks of treatment using the low-intensity pulsed ultrasound,the fusion in the bone grafting area of observation group was good.There was the relatively dense fusion area between the right transverse process and artificial bone.The left transverse process had been completely fused,with the clear bone trabecula through the fusion area.There was no significant fusion sign in the control group.According to the fusion comparison between two groups,the fusion rale of the observation group was 83.3%and it was significantly higher than the one of the control group(37.5%).Results of the comparison were statistically significant(P<0.05).The number of chondrocytes and the increase in the relative gray-scale in the fusion area of the iliac observation group were significantly higher than ones of the iliac control group(P<0.05).The number of chondrocytes and the increase in the relative gray-scale in the fusion area of the artificial bone observation group were significantly higher than ones of the artificial bone control group(P<0.05).The expression of IL-1.IL-6 and IL-17 4 weeks after the treatment of the observation group was significantly lower than the one of the control group,with the statistical significance(P<0.05).It indicated that the treatment of low-intensity pulsed ultrasound could reduce the expression level of inflammatory factors.Conclusions:The low-intensity pulsed ultrasound can significantly increase the bone grafting fusion rate of the rabbit's posterolateral lumbar fusion.The possible mechanism is that it promotes the lumbar posterolateral endochondral ossification and reduces the inflammatory reaction.

Effect of Low-Intensity Pulsed Ultrasound on Ischaemic Heart Disease Patients (Novel Technique)

Ischaemic Heart Disease (IHD) or Coronary heart disease means that the heart is not getting enough blood and oxygen supply through the coronary arteries. The most common cause of this disease is the process of atherosclerosis in the coronary arteries. Although significant progress has been made in the management of ischaemic heart disease (IHD) The number of severe IHD patients is increasing. The treatment options for IHD have not changed much over the last three decades, which is divided between medications, coronary Angioplasty and Coronary artery bypass surgery. Thus it was crucial to develop new, non-invasive therapeutic strategies in case of Failure of medical or interventional therapy or in case patient is not fit for surgery or angioplasty. In this study, we are pleased to reveal a novel technique that was carried out on a human model. We aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of patients with Ischaemic Heart Disease. We have set up the inclusion and exclusion criteria, the treatment protocol of LIPUS on IHD patients. In this limited group of IHD patients, We found promising clinical results and improvement on myocardial functions.

The Effect of Material Surface Microstructure on the Enhancement of Bone-Bonding Ability of a Hydroxyapatite-Implant by Low-Intensity Pulsed Ultrasound (LIPUS)

Excellent firm bonding between the biomaterials and bone tissue (osseointegration and osteo-conductivity) has been desired for the stability in vivo of dental implants and artificial joints. Much has been learned about this concept, which has led to significant improvements in the design and surface modification of implants in the field of implant dentistry, orthopedic surgery. We have already reported that low-intensity pulsed ultrasound (LIPUS) irradiation can accelerate the bone bonding ability of the bio-conductive materials such as bioactive titanium and hydroxyapatite implant. However, it is still unclear whether the LIPUS could have same effect to different types of the bioactive-materials. Therefore, in this study, the differences of bone-like hydroxyapatite formation on some kind of hydroxyapatite surface in simulated body fluid (SBF) under the LIPUS irradiation were investigated. Two kinds of hydroxyapatite samples immersed in SBF was exposed to ultrasound waves, the bone-like apatite on the surface was analyzed by Scanning electron microscopy and X-ray diffraction. As a result, the enhancement of hydroxyapatite formation on the surface by LIPUS was confirmed, the initial epitaxial nucleation and crystal growth of apatite depended on crystal structure of the surface of matrix materials.

L-Type Calcium Channel Modulates Low-Intensity Pulsed Ultrasound-Induced Excitation in Cultured Hippocampal Neurons

As a noninvasive technique,ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo.The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons.However,the underlying mechanism of low-intensity pulsed ultrasound(LIPUS)-induced neuro-modulation effects is still unclear.Here,we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca^(2+)homeostasis in cultured hippocampal neurons.By whole-cell patch clamp recording,we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents(sEPSCs)and also increases the amplitude of sEPSCs in hippocampal neurons.This phenomenon lasts for>10 min after LIPUS exposure.Together with Ca^(2+)imaging,we clarified that LIPUS increases the[Ca^(2+)]cyto level by facilitating L-type Ca^(2+)channels(LTCCs).In addition,due to the[Ca^(2+)]cyto elevation by LIPUS exposure,the Ca^(2+)-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein expression.Our work suggests that LIPUS regulates neuronal activity in a Ca^(2+)-dependent manner via LTCCs.This may also explain the multi-activation effects of LIPUS beyond neurons.LIPUS stimulation potentiates spontaneous neuronal activity by increasing Ca^(2+)influx.

Extracellular vesicles derived from human dental mesenchymal stem cells stimulated with low-intensity pulsed ultrasound alleviate inflammation-induced bone loss in a mouse model of periodontitis

Extracellular vesicles(EVs)derived from mesenchymal stem cells(MSCs)have emerged as a new mode of intercellular crosstalk and are responsible for many of the thera-peutic effects of MSCs.To promote the application of MSC-EVs,recent studies have focused on the manipulation of MSCs to improve the production of EVs and EV-mediated activities.The current paper details an optimization method using non-invasive low-intensity pulsed ul-trasound(LIPUS)as the stimulation for improving oral MSC-EV production and effectiveness.Stem cells from apical papilla(SCAP),a type of oral mesenchymal stem cell,displayed inten-sity-dependent pro-osteogenic and anti-inflammatory responses to LIPUS without significant cytotoxicity or apoptosis.The stimuli increased the secretion of EVs by promoting the expres-sion of neutral sphingomyelinases in SCAP.In addition,EVs from LIPUS-induced SCAP exhibited stronger efficacy in promoting the osteogenic differentiation and anti-inflammation of peri-odontal ligament cells in vitro and alleviating oral inflammatory bone loss in vivo.In addition,LIPUS stimulation affected the physical characteristics and miRNA cargo of SCAP-EVs.Further investigations indicated that miR-935 is an important mediator of the pro-osteogenic and anti-inflammatory capabilities of LIPUS-induced SCAP-EVs.Taken together,these findings demonstrate that LIPUS is a simple and effective physical method to optimize SCAP-EV produc-tion and efficacy.

Effects of low-intensity pulsed ultrasound in repairing injured articular cartilage

Objective: To investigate the effects of low-intensity pulsed ultrasound in repairing injured articular cartilage. Methods: Ten adult New Zealand rabbits with bilateral full-thickness osteochondral defects on the cartilage surface of intercondylar fossas were used in this study. The wounds in the left knees were treated with low-intensity pulsed ultrasound as the experimental group. The right knees received no treatment as the control group. All the animals were killed at 8 weeks after injury and the tissues in the wounds were collected for gross appearance grading, histological grading and proteoglycan quantity. Results: The scores of the gross appearance grades, histological grades and the optical density of toluidine blue of the tissues in the experimental group were significantly higher than those of the controls at 8 weeks after injury (P<(0.05)). Conclusions: Low-intensity pulsed ultrasound can accelerate the repair of injured articular cartilage.

Improved activity of MC3T3-E1 cells by the exciting piezoelectric BaTiO_(3)/TC4 using low-intensity pulsed ultrasound

Developing bioactive materials for bone implants to enhance bone healing and bone growth has for years been the focus of clinical research.Barium titanate(BT)is an electroactive material that can generate electrical signals in response to applied mechanical forces.In this study,a BT piezoelectric ceramic coating was synthesized on the surface of a TC4 titanium alloy,forming a BT/TC4 material,and low-intensity pulsed ultrasound(LIPUS)was then applied as a mechanical stimulus.The combined effects on the biological responses of MC3T3-E1 cells were investigated.Results of scanning electron microscopy,energy-dispersive X-ray spectroscopy,and X-ray diffraction showed that an uniform nanospheres-shaped BT coating was formed on TC4 substrate.Piezoelectric behaviors were observed using piezoelectric force microscopy with the piezoelectric coefficient d_(33)of 0.42 pC/N.Electrochemical measures indicated that LIPUS-stimulated BT/TC4 materials could produce a microcurrent of approximately 10μA/cm^(2).In vitro,the greatest osteogenesis(cell adhesion,proliferation,and osteogenic differentiation)was found in MC3T3-E1 cells when BT/TC4 was stimulated using LIPUS.Furthermore,the intracellular calcium ion concentration increased in these cells,possibly because opening of the L-type calcium ion channels was promoted and expression of the Ca_(V)1.2 protein was increased.Therefore,the piezoelectric BT/TC4 material with LIPUS loading synergistically promoted osteogenesis,rending it a potential treatment for early stage formation of reliable bone-implant contact.

Low-intensity pulsed ultrasound for regenerating peripheral nerves:potential for penile nerve

Peripheral nerve damage,such as that found after surgery or trauma,is a substantial clinical challenge.Much research continues in attempts to improve outcomes after peripheral nerve damage and to promote nerve repair after injury.In recent years,low-intensity pulsed ultrasound(LIPUS)has been studied as a potential method of stimulating peripheral nerve regeneration.In this review,the physiology of peripheral nerve regeneration is reviewed,and the experiments employing LIPUS to improve peripheral nerve regeneration are discussed.Application of LIPUS following nerve surgery may promote nerve regeneration and improve functional outcomes through a variety of proposed mechanisms.These include an increase of neurotrophic factors,Schwann cell(SC)activation,cellular signaling activations,and induction of mitosis.We searched PubMed for articles related to these topics in both in vitro and in vivo animal research models.We found numerous studies,suggesting that LIPUS following nerve surgery promotes nerve regeneration and improves functional outcomes.Based on these findings,LIPUS could be a novel and valuable treatment for nerve injury-induced erectile dysfunction.

Low-intensity pulsed ultrasound therapy: a potential strategy to stimulate tendon-bone junction healing

Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem. Successfulanterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel. En-hancement of graft healing to bone is important to facilitate early aggressive rehabilitation and a rapid return topre-injury activity levels. No convenient, effective or inexpensive procedures exist to enhance tendon-bone (T-B)healing after surgery. Low-intensity pulsed ultrasound (LIPUS) improves local blood perfusion and angiogenesis,stimulates cartilage maturation, enhances differentiation and proliferation of osteoblasts, and motivates osteogenic differentiation of mesenchymal stem cells (MSCs), and therefore, appears to be a potential non-invasive tool for T-Bhealing in early stage of rehabilitation of ACL reconstruction. It is conceivable that LIPUS could be used to stimulateT-B tunnel healing in the home, with the aim of accelerating rehabilitation and an earlier return to normal activities inthe near future. The purpose of this review is to demonstrate how LIPUS stimulates T-B healing at the cellular andmolecular levels, describe studies in animal models, and provide a future direction for research.

Low-intensity pulsed ultrasound stimulates proliferation of stem/progenitor cells: what we need to know to translate basic science research into clinical applications

Low-intensity pulsed ultrasound (LIPUS) is a promising therapy that has been increasingly explored in basic research and clinical applications. LIPUS is an appealing therapeutic option as it is a noninvasive treatment that has many advantages, including no risk of infection or tissue damage and no known adverse reactions. LIPUS has been shown to have many benefits including promotion of tissue healing, angiogenesis, and tissue regeneration;inhibition of inflammation and pain relief;and stimulation of cell proliferation and differentiation. The biophysical mechanisms of LIPUS remain unclear and the studies are ongoing. In recent years, more and more research has focused on the relationship between LIPUS and stem/progenitor cells. A comprehensive search of the PubMed and Embase databases to July 2020 was performed. LIPUS has many effects on stem cells. Studies show that LIPUS can stimulate stem cells in vitro;promote stem cell proliferation, differentiation, and migration;maintain stem cell activity;alleviate the problems of insufficient seed cell source, differentiation, and maturation;and circumvent the low efficiency of stem cell transplantation. The mechanisms involved in the effects of LIPUS are not fully understood, but the effects demonstrated in studies thus far have been favorable. Much additional research is needed before LIPUS can progress from basic science research to large-scale clinical dissemination and application.

Low-intensity pulsed ultrasound prompts tissue-engineered bone formation after implantation surgery

Background A practical problem impeding clinical translation is the limited bone formation seen in artificial bone grafts.Low-pressure/vacuum seeding and dynamic culturing in bioreactors have led to a greater penetration into the scaffolds,enhanced production of bone marrow cells,and improved tissue-engineered bone formation.The goal of this study was to promote more extensive bone formation in the composites of porous ceramics and bone marrow stromal cells （BMSCs）.Methods BMSCs/β-tricalcium phosphate （β-TCP） composites were subcultured for 2 weeks and then subcutaneously implanted into syngeneic rats that were split into a low-intensity pulsed ultrasound （LIPUS） treatment group and a control group.These implants were harvested at 5,10,25,and 50 days after implantation.The samples were then biomechanically tested and analyzed for alkaline phosphate （ALP） activity and osteocalcin （OCN） content and were also observed by light microscopy.Results The levels of ALP activity and OCN content in the composites were significantly higher in the LIPUS group than in the control group.Histomorphometric analysis revealed a greater degree of soft tissue repair,increased blood flow,better angiogenesis,and more extensive bone formation in the LIPUS groups than in the controls.No significant difference in the compressive strength was found between the two groups.Conclusion LIPUS treatment appears to enhance bone formation and angiogenesis in the BMSCs/β3-TCP composites.

Low-Intensity Pulsed Ultrasound Promote Schwann Cells Pro-Myelination Activities and Neurite Outgrowth of Dorsal Root Ganglion Neurons

In this study,we investigate how Schwann cells and dorsal root ganglion(DRG)neurons response to direct low-intensity pulsed ultrasound(LIPUS)stimuli in vitro.Primary Schwann cells and DRG were isolated from rat sciatic nerve and spine,respectively.LIPUS with varied dose of intensity(low:250 mW/cm2,medium:500 m W/cm2,high:750 m W/cm2)were applied 5 min per time for every other day,and pro-myelination indicators of Schwann cell as well as neurite outgrowth of dorsal root ganglion neurons were analyzed.Our results demonstrated that LIPUS promoted Schwann cells activity and proliferation from day 3 at the highest intensity,and day 5 at all intensities.In addition,LIPUS boosted pro-myelination activities of Schwann cells,as evidenced by increased cell population that positive for immunohistochemical staining against S100,nerve growth factor receptor(NGFR)p75,glial fibrillary acidic protein(GFAP),myelin protein zero(P0),as well as up-regulation of GFAP,Protein 0,nerve growth factor(NGF),and brain derived neurotrophic factor(BDNF)genes.Furthermore,LIPUS significantly enhanced the neurite outgrowth of DRG,with the highest intensity exhibiting longest neurite outgrowth.Taken together,our results strongly improve the understanding of cellular mechanisms of ultrasonic therapies for peripheral nerve repair.

低频超声联合曲安奈德对金黄地鼠颊黏膜溃疡愈合的影响

目的:研究低频超声联合曲安奈德对金黄地鼠实验性口腔溃疡愈合时间,以及溃疡组织中超氧化物歧化酶(superoxide dismutase,SOD)和微量丙二醛(malondialdehyde,MDA)含量的影响。方法:将60只金黄地鼠随机分为5组,1组为基线组(包括正常基线组和溃疡基线组,各6只),另外4组为实验组(低频超声+药物组、单独超声组、单独药物组和空白对照组),每组12只,各组通过"氧自由基损伤法"建立口腔溃疡模型。末次处理24 h后观察溃疡愈合情况,并检测溃疡组织中的SOD活性及MDA含量。采用SPSS 20.0软件包对数据进行统计学分析。结果:低频超声+药物组较单独超声组、单独药物组及空白对照组溃疡愈合时间显著缩短。末次处理24 h后SOD检测结果显示,低频超声+药物组[(2.32±0.30)U/mgprot]较溃疡基线组[(1.48±0.29)U/mgprot]、单独超声组[(1.83±0.15)U/mgprot]、单独药物组[(1.76±0.25)U/mgprot]及空白对照组[(1.71±0.18)U/mgprot]显著增高(P<0.05);低频超声+药物组MDA含量[(8.17±0.21)nmol/mgprot]较溃疡基线组[(9.41±0.22)nmol/mgprot]、单独超声组[(9.00±0.44)nmol/mgprot]、单独药物组[(9.04±0.43)nmol/mgprot]及空白对照组[(9.03±0.46)nmol/mgprot]显著降低(P<0.05)。溃疡愈合后SOD活性及MDA含量检测显示,低频超声+药物组、单独超声组、单独药物组及空白对照组与正常基线组相比无显著差异(P>0.05)。结论:低频超声协同曲安奈德能显著缩短溃疡愈合时间,增加溃疡组织中SOD活性,降低MDA含量,对溃疡的愈合有一定的促进作用。

脉冲与连续高强度聚焦超声对离体牛肝表面消融的效果比较

目的比较脉冲高强度聚焦超声(pulsed high-intensity focused ultrasound,PHIFU)与连续高强度聚焦超声(continuous high-intensity focused ultrasound,CHIFU)表面消融模式的消融效果,探讨优化HIFU表面消融模式的辐照策略。方法将40块牛肝组织按辐照方式不同分为A组(30块,PHIFU表面消融模式)和B组(10块,CHIFU表面消融模式),A组再按占空比均分为A1(10%)、A2(30%)、A3(50%)3个亚组,每个亚组10块。B超监控下,A、B组分别采用PHIFU与CHIFU表面消融模式对靶区进行辐照,辐照同时记录靶区内部温度,辐照后观察靶区边缘及其内、外未辐照区损伤情况,测算能效因子并分析温度时间曲线。结果能效因子:A1组<A2组<A3组<B组。靶区外部:仅B组出现明显热损伤;靶区边缘:各组均可形成封闭隔离带,A1组呈液性坏死,其余组呈凝固性坏死;靶区内部:组织损伤程度随占空比增大而增大。内部温度:除A1组,其余组最高温度均超过60℃。结论 PHIFU较CHIFU在提高消融效率、减少靶区外组织损伤上更有优势。PHIFU表面消融时,调整占空比可改变靶组织内部未辐照区的温升及损伤情况。

PHIFU辐照晶状体致凝固性坏死与空化关系的实验研究

目的:研究相同剂量,不同辐照参数的脉冲高强度聚焦超声(pulsed high intensity focused ultrasound,PHIFU)辐照牛眼晶状体所致凝固性坏死的变化过程及其与空化效应的关系,探讨何种方式辐照效果最佳。方法:用不同声功率和占空比的PHIFU(A组对照组:60 W-100%,B组:120 W-50%,C组:240 W-25%,D组:500 W-12%)辐照牛眼晶状体,辐照过程中使用高速摄像系统实时拍摄凝固性坏死的变化,被动空化检测(passive cavitation detection,PCD)系统记录焦域处发出的声散射信息,分析辐照过程中两者之间的关系,并比较各参数辐照效果。结果:各组均发生凝固性坏死,C、D 2组相应RMS幅值在辐照开始时就增高,其凝固性坏死出现平均时间分别为(2.63±0.71)s、(2.45±0.68)s。其中D组凝固性坏死出现所需时间最短,坏死体积最大,能效因子(energy efficiency factor,EEF)值最小,空化发生剧烈。结论:总剂量相同的PHIFU辐照下,声功率500 W,占空比12%的辐照效果最好。空化效应的发生要早于凝固性坏死的出现。

Low‐intensity pulsed ultrasound ameliorates angiotensin II-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway

Objective:Cardiac hypertrophy and fibrosis are major pathological manifestations observed in left ventricular remodeling induced by angiotensin II(AngII).Low-intensity pulsed ultrasound(LIPUS)has been reported to ameliorate cardiac dysfunction and myocardial fibrosis in myocardial infarction(MI)through mechano-transduction and its downstream pathways.In this study,we aimed to investigate whether LIPUS could exert a protective effect by ameliorating AngII-induced cardiac hypertrophy and fibrosis and if so,to further elucidate the underlying molecular mechanisms.Methods:We used AngII to mimic animal and cell culture models of cardiac hypertrophy and fibrosis.LIPUS irradiation was applied in vivo for 20 min every 2 d from one week before mini-pump implantation to four weeks after mini-pump implantation,and in vitro for 20 min on each of two occasions 6 h apart.Cardiac hypertrophy and fibrosis levels were then evaluated by echocardiographic,histopathological,and molecular biological methods.Results:Our results showed that LIPUS could ameliorate left ventricular remodeling in vivo and cardiac fibrosis in vitro by reducing AngII-induced release of inflammatory cytokines,but the protective effects on cardiac hypertrophy were limited in vitro.Given that LIPUS increased the expression of caveolin-1 in response to mechanical stimulation,we inhibited caveolin-1 activity with pyrazolopyrimidine 2(pp2)in vivo and in vitro.LIPUS-induced downregulation of inflammation was reversed and the anti-fibrotic effects of LIPUS were absent.Conclusions:These results indicated that LIPUS could ameliorate AngII-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway,providing new insights for the development of novel therapeutic apparatus in clinical practice.

Effect of LIPUS on inflammatory factors, cell apoptosis and integrin signaling pathway in osteoarthritis animal models

Objective:To study the effect of low-intensity pulsed ultrasound (LIPUS) on inflammatory factors, cell apoptosis and integrin signaling pathway in osteoarthritis animal models. Methods:Male New Zealand white rabbits were selected as the experimental animals and randomly divided into sham group, osteoarthritis model group (OA group) and LIPUS intervention group (LIPUS group), animal models with osteoarthritis in hind limb knee joint were established and then given LIPUS intervention. 6 weeks after the intervention, the articular cartilage was separated to detect the expression of inflammatory factors, cell apoptosis molecules and integrin signaling pathway molecules.Results: OPN, NO, IL-1β, TNF-α, Fas, FasL, LC3-II, Beclin-1, Integrinβ1, FAK, ERK1/2, JNK, p38MAPK, MMP-1 and MMP-3 protein expression in articular cartilage of OA group were significantly higher than those of Sham group while Col-I and Col-II protein expression were significantly lower than those of Sham group;OPN, NO, IL-1β, TNF-α, Fas, FasL, LC3-II, Beclin-1, Integrinβ1, FAK, ERK1/2, JNK, p38MAPK, MMP-1 and MMP-3 protein expression in articular cartilage of LIPUS group were significantly lower than those of OA group while Col-I and Col-II protein expression were significantly higher than those of OA group.Conclusion:LIPUS has inhibiting effect on the inflammation, apoptosis and integrin signaling pathway in articular cartilage of osteoarthritis animal models, and it can promote the repair of articular cartilage.