Low-intensity pulsed ultrasound promotes osteoarthritic cartilage regeneration by BMSC-derived exosomes via modulating the NF-κB signaling pathway

Objective. Studies regarding the combination of ultrasound and transcutaneous electrical nerve stimulation (TENS) are rarely reported. In this study, we aimed to elucidate the efficacy and safety of a stimulator using low-intensity pulsed ultrasound (LIPUS) combined with TENS in patients with painful knee osteoarthritis (OA). We evaluated the effectiveness of this therapy against pain, physical function, and cartilage regeneration. Moreover, we aim to prove the superiority of the effects of LIPUS combined with TENS therapy compared with only TENS therapy.Methods. Of the 40 included patients, aged 45–85 years with painful knee OA, 20 patients received only TENS therapy and 20 patients received LIPUS combined with TENS therapy for 8 weeks (a total of more than 80 treatment sessions). We evaluated visual analogue scale (VAS), Western Ontario and McMaster Universities (WOMAC) osteoarthritis index, MOS 36-Item Short-Form Health Survey (SF-36), and femoral articular cartilage (FAC) thickness. The evaluation was performed at three visits: visit 1 (V1, pretreatment, within 28 days after screening), visit 2 (V2, posttreatment period 1, ±3 days after treatment), and visit 3 (V3, posttreatment period 2, 21 ± 3 days after treatment).Results. We expected that LIPUS combined with TENS therapy would be superior to only TENS therapy. However, there was no significant difference between the two therapies. In the within-group comparison, both treatments (only TENS therapy and LIPUS with TENS therapy) demonstrated statistical differences from baseline values for pain and physical function outcomes. FAC thickness showed no significant differences after treatment in both groups.Conclusion. The effects of a stimulator using LIPUS with TENS on pain relief and functional improvement were not superior to the only TENS therapy. Cartilage regeneration, which was expected as an additional benefit of LIPUS, was also not significantly evident. Therefore, further investigation is warranted to determine whether the combination therapy is beneficial. This trial is registered withKCT0003883.

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Low Intensity Pulsed Ultrasound (LIPUS) Influences the Multilineage Differentiation of Mesenchymal Stem and Progenitor Cell Lines through ROCK-Cot/Tpl2-MEK-ERK Signaling Pathway

Journal of Biological Chemistry ◽

10.1074/jbc.m113.546382 ◽

2014 ◽

Vol 289 (15) ◽

pp. 10330-10344 ◽

Cited By ~ 66

Author(s):

Joji Kusuyama ◽

Kenjiro Bandow ◽

Mitsuo Shamoto ◽

Kyoko Kakimoto ◽

Tomokazu Ohnishi ◽

...

Keyword(s):

Signaling Pathway ◽

Cell Lines ◽

Progenitor Cell ◽

Erk Signaling ◽

Multilineage Differentiation ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity

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Low-intensity pulsed ultrasound promotes Schwann cell viability and proliferation via the GSK-3β/β-catenin signaling pathway

International Journal of Biological Sciences ◽

10.7150/ijbs.22409 ◽

2018 ◽

Vol 14 (5) ◽

pp. 497-507 ◽

Cited By ~ 6

Author(s):

Cong Ren ◽

Xiaohui Chen ◽

Ning Du ◽

Shuo Geng ◽

Yingying Hu ◽

...

Keyword(s):

Schwann Cell ◽

Cell Viability ◽

Signaling Pathway ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Gsk 3Β

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Effects of Low-Intensity Pulsed Ultrasound on the Proliferation of Human Umbilical Cord Mesenchymal Stem Cells and Their Chondrogenic Differentiation via Bmp2 /Smad Signaling Pathway

10.21203/rs.3.rs-122372/v1 ◽

2020 ◽

Author(s):

Xuhong JIN ◽

Hejie Wang ◽

Jiaju Che ◽

Xiafu Chen ◽

Dengao Huang ◽

...

Keyword(s):

Signaling Pathway ◽

Chondrogenic Differentiation ◽

Blue Staining ◽

Control Group ◽

Human Umbilical Cord ◽

Pulsed Ultrasound ◽

Low Intensity Pulsed Ultrasound ◽

Low Intensity ◽

Proliferation Activity ◽

Smad Signaling Pathway

Abstract BackgroundAlthough Low-intensity pulsed ultrasound (LIPUS) regiment has been applied to the treatment of cartilage injury clinically, the effect of LIPUS stress loading on the proliferation and differentiation of hUCMSCs is still controversial. Yet the specific mechanical mechanism of LIPUS stimulates cartilage differentiation of hUCMSCs has not been clarified.ObjectiveTo investigate the effects of low intensity pulsed ultrasound (LIPUS) on proliferation and chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUCMSCs) via BMP2 /smad signaling pathway in vitro.MethodThe hUCMSCs at P4 were randomly divided into control group(no LIPUS), L30 group (30mW/cm2), L50 group (50mW/cm2), L80 group (80mW/cm2), each LIPUS group respectively loaded 5, 10, 20 min/d, the cell proliferation activity was detected by CCK-8 assay after continuous irradiation for 5 days. For chondrogenic differentiation, hUCMSCs were divided 4 groups as follows: control group, Noggin group, LIPUS group, Noggin+LIPUS group, LIPUS irradiation was given 50w/cm2, 5min/d. Cartilage formation after 3 weeks was evaluated by Alician blue staining for GAG and COL II immunohistochemical staining. Furthermore, RT-PCR analysis of Sox-9, COL II Aggrecan, BMP2, Smad1, Smad5 and Smad9. Result： (1) The proliferation activity of L50 group(50w/cm2 , 5min/d) was noticeably higher compared with other groups, Alcian blue staining of GAG , COL II fluorescent staining in the LIPUS group were much stronger, quantitative RT-PCR assays showed that the expression of COL II, GAG, Sox-9, smad1, smad5 and smad9 in LIPUS group was significantly increased. Conclusion：The suitable LIPUS irradiation can promote cell proliferation, 50mW/cm2 intensity at 5min/d is most significant. And it can promote chondrogenesis of hUCMSCs via upregulating MP2 /smads signaling pathway.

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