Low-intensity pulsed ultrasound activates the PI3K/Akt pathway and stimulates the growth of chondrocytes in 3D-cultures: a basic science study

Takeuchi, Ryohei; Ryo, Akihide; Komitsu, Noriko; Mikuni-Takagaki, Yuko; Fukui, Akihiro; Takagi, Yuta; Shiraishi, Toshihiko; Morishita, Shin; Yamazaki, Yuko; Kumagai, Ken; Aoki, Ichiro; Saito, T.

doi:10.1186/ar2451

Cited by 114 publications

(84 citation statements)

References 36 publications

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“…In vitro experiments have demonstrated that LIPUS stimulation affects mouse and rat osteoblast differentiation without influencing proliferation (8,9). Although the mechanisms involved have not been elucidated, LIPUS transmits signals into the cell via an integrin that acts as a mechanoreceptor on the cell membrane (16). The integrin/Ras/MAPK pathway is known to be a general pathway involved in cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Effects of low-intensity pulsed ultrasound on osteosarcoma and cancer cells

et al. 2012

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Abstract. Metastatic bone tumors cause pain and pathological fractures due to bone destruction. If we could enhance new osteogenic activities and prevent progression of osteolytic change by malignant cells, patients could achieve satisfactory activity of daily living. Low-intensity pulsed ultrasound (LIPUS), which leads to bone formation by osteoblasts, has been used for the treatment of fractures. LIPUS has been reported to enhance the effect of an anticancer drug on lymphoma and liver cancer cells. However, there have been no reports of proliferation, vascularization and migration effects on cancer cells. In this study, we investigated the effects of LIPUS treatment on cancer and osteosarcoma cells and specifically whether it promotes bone formation without accelerating proliferation of tumor cells. We used MC3T3-E1 cells, a mouse osteoblast cell line, LM8, a mouse osteosarcoma cell line, SaOS2, a human osteosarcoma cell line, 786-O, a human renal cancer cell line, PC-3, a human prostate cancer cell line, and A549, a human lung cancer cell line. The expression of extracellular signal-regulated kinase (ERK1/2), Akt, β-catenin, vascular endothelial growth factor (VEGF), and cell migration were analyzed. LIPUS stimulation did not affect proliferation of all the cells examined. The phosphorylation of ERK1/2 and Akt was induced by LIPUS stimulation in MC3T3-E1, LM8, SaOS2 and A549 cells, but not in PC-3 and 786-O cells. LIPUS stimulation did not significantly increase β-catenin. VEGF protein levels and cell migration were significantly increased only in MC3T3-E1 cells. It may be concluded that LIPUS stimulation on metastatic bone tumors induces differentiation of osteoblasts without proliferation of tumor cells. Our study suggests that LIPUS may be a new method of treatment without surgery for metastatic bone tumors.

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Section: Discussionmentioning

confidence: 99%

Effects of low-intensity pulsed ultrasound on osteosarcoma and cancer cells

et al. 2012

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“…It seems that the splicing protein TASR-1 attributes in removing exon 2 from Col2A [44]. Probably ultrasound mediated these effects via integrins and activativation of MAPK signaling and phosphorylation pathway [45]. Previous studies showed that phosphorylation modulates splicing proteins function [46] and stress stimulus resulted in changes splicing factors [46][47][48][49].…”

Section: Discussionmentioning

confidence: 99%

Effects of Low Intensity Ultrasound on the Chondrogenic Differentiation of Adult Stem Cells From Adipose Tissue

Shafaei

Esmaeili

Mardani

et al. 2016

Zahedan J Res Med Sci

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Background: Adult stem cells from adipose tissue can be used in tissue engineering because of their capacity to differentiate into chondrocytes. Low intensity ultrasound (LIUS) as a physical chondrogenic inducer differentiates adipose stem cells (ASC) into chondrocyte the same as transforming growth factor-β (TGFβ). However the stage of differentiation and hypertrophy of chondrocytes by LIUS have not yet been studied. Objectives: The aim of this study was to determine the effect of LIUS on hypertrophic states of differentiated chondrocytes. Materials and Methods: In this experimental study, ASCs were cultured in chondrogenic differentiation medium (10 ng/mL of TGFβ) with or without LIUS stimulation for two weeks. The ultrasound signal was applied at an intensity of 200 mW/cm 2 for 10

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“…The PC is a characteristic structure of the endochondral ossification processes, it is composed of highly organized cartilaginous tissue, it is located between the epiphysis and the diaphysis of the long bones and whose main function is the modulation of the longitudinal growth of the bone (van der Eerden et al, 2003). The PC is divided into three zones, each with distinctive morphological characteristics (Mackie et al, 2008), From epiphysis to diaphysis, we will find:…”

Section: Introductionmentioning

confidence: 99%

“…Nolte et al (2001) performed a morphohistological analysis on in vitro cultures of metatarsals after the application of LIPUS for 6 days, observing changes in the rate of bone growth expressed in an increase in the length of the diaphysial ossification center. It was hypothesized that this result could be explained by the activation of the PI3K / Akt pathway as the trigger for proliferation of chondrocytes mediated by LIPUS (Takeuchi et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Effects of Underwater Lipus on the Morphohistology of the CF-1 Mice Growth Plate in Late Lactation Stage

Henríquez

Yuing

Pallauta³

et al. 2017

Int. J. Morphol.

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Morphol., 35(4):1351Morphol., 35(4): -1358Morphol., 35(4): , 2017. SUMMARY:Ultrasound is one of the most used tools in physiotherapy, its LIPUS modality allows to treat musculoskeletal injuries, but like the conventional ultrasound it is contraindicated its application in areas close to growth cartilage by a possible closure of this one. In the literature there is no conclusive evidence of this contraindication, so the objective of the present study is to evaluate the effects of doses equivalent to underwater LIPUS on the histomorphometry of the proximal tibial epiphysis growth plate in an animal model. LIPUS was applied in underwater mode in the right pelvic limb to 8 mice in p 15 for 4 days, 2 times a day. On completion of 8 sessions the histology of the stimulated limb growth plate was sacrificed and the histology. When evaluating the histomorphometry of the plaque, a significant increase in the thickness and area of the proliferative zone stimulated with LIPUS (p = 0.048) was observed. In the hypertrophic area were observed no significant differences in thickness or areas, but in the hypertrophic area there were significant changes in the histological organization, observing a significant increase of the entire columns in the stimulated plaque (p = 0.04). LIPUS in underwater modality modifies the histomorphometry of the proximal epiphyseal PC of the tibia of rodents in the late postnatal stage, promoting proliferation and columnar organization in the proliferative and hypertrophic zone, respectively.

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Low-intensity pulsed ultrasound activates the PI3K/Akt pathway and stimulates the growth of chondrocytes in 3D-cultures: a basic science study

Cited by 114 publications

References 36 publications

Effects of low-intensity pulsed ultrasound on osteosarcoma and cancer cells

Effects of low-intensity pulsed ultrasound on osteosarcoma and cancer cells

Effects of Low Intensity Ultrasound on the Chondrogenic Differentiation of Adult Stem Cells From Adipose Tissue

Effects of Underwater Lipus on the Morphohistology of the CF-1 Mice Growth Plate in Late Lactation Stage

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