Low intensity pulsed ultrasound alleviates synovial fibrosis in osteoarthritis via the PI3K/AKT pathway

Abstract Previous studies have reported that low-intensity pulsed ultrasound (LIPUS) can alleviate cartilage degradation in osteoarthritis (OA). However, the functions and mechanisms of LIPUS in synovial fibrosis with OA require further study. To investigate the role of the PI3K/AKT signaling pathwa...

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Main Authors: Qing Liao, Jun Chen, Gang Liu
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-92413-x
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author Qing Liao
Jun Chen
Gang Liu
author_facet Qing Liao
Jun Chen
Gang Liu
author_sort Qing Liao
collection DOAJ
description Abstract Previous studies have reported that low-intensity pulsed ultrasound (LIPUS) can alleviate cartilage degradation in osteoarthritis (OA). However, the functions and mechanisms of LIPUS in synovial fibrosis with OA require further study. To investigate the role of the PI3K/AKT signaling pathway in synovial fibrosis and in LIPUS treatment in synovial fibrosis, a TGF-β stimulated rat FLS cell model and a rat OA animal model based on anterior cruciate ligament transection (ACLT) and partial medial meniscectomy (MMx) were used. The results revealed that LIPUS delayed the progression of OA. Masson staining revealed that LIPUS reduced the collagen deposition of synovial tissue in OA rats. Correspondingly, immunofluorescence demonstrated that LIPUS significantly downregulated the expression of α-SMA, Col1a1 and Col3a1 in OA rats. Moreover, TGF-β stimulation upregulated fibrosis markers at the mRNA and protein levels in FLS, as well as increased phosphorylation-dependent activation of the PI3K/Akt pathway. 740Y-P was found to promote the fibrotic change of FLS induced by TGF-β, but LY294002 reduced its expression. However, LIPUS inhibits the fibrotic change and activation of the PI3K/Akt pathway in FLS under stimulation of TGF-β. In conclusion, LIPUS alleviates synovial fibrosis by blocking the PI3K/AKT pathway.
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spelling doaj-art-1104a4b2a98b433cbdb9059870f792832025-08-20T02:10:53ZengNature PortfolioScientific Reports2045-23222025-03-0115111510.1038/s41598-025-92413-xLow intensity pulsed ultrasound alleviates synovial fibrosis in osteoarthritis via the PI3K/AKT pathwayQing Liao0Jun Chen1Gang Liu2School of Traditional Chinese Medicine, Southern Medical UniversityDepartment of Rehabilitation Medicine, Nanfang Hospital of Southern Medical UniversityDepartment of Rehabilitation Medicine, Nanfang Hospital of Southern Medical UniversityAbstract Previous studies have reported that low-intensity pulsed ultrasound (LIPUS) can alleviate cartilage degradation in osteoarthritis (OA). However, the functions and mechanisms of LIPUS in synovial fibrosis with OA require further study. To investigate the role of the PI3K/AKT signaling pathway in synovial fibrosis and in LIPUS treatment in synovial fibrosis, a TGF-β stimulated rat FLS cell model and a rat OA animal model based on anterior cruciate ligament transection (ACLT) and partial medial meniscectomy (MMx) were used. The results revealed that LIPUS delayed the progression of OA. Masson staining revealed that LIPUS reduced the collagen deposition of synovial tissue in OA rats. Correspondingly, immunofluorescence demonstrated that LIPUS significantly downregulated the expression of α-SMA, Col1a1 and Col3a1 in OA rats. Moreover, TGF-β stimulation upregulated fibrosis markers at the mRNA and protein levels in FLS, as well as increased phosphorylation-dependent activation of the PI3K/Akt pathway. 740Y-P was found to promote the fibrotic change of FLS induced by TGF-β, but LY294002 reduced its expression. However, LIPUS inhibits the fibrotic change and activation of the PI3K/Akt pathway in FLS under stimulation of TGF-β. In conclusion, LIPUS alleviates synovial fibrosis by blocking the PI3K/AKT pathway.https://doi.org/10.1038/s41598-025-92413-xOsteoarthritisSynovial fibrosisLow-intensity pulsed ultrasoundPI3K/AKT signaling pathwaySynovitisFibroblast-like synoviocyte
spellingShingle Qing Liao
Jun Chen
Gang Liu
Low intensity pulsed ultrasound alleviates synovial fibrosis in osteoarthritis via the PI3K/AKT pathway
Scientific Reports
Osteoarthritis
Synovial fibrosis
Low-intensity pulsed ultrasound
PI3K/AKT signaling pathway
Synovitis
Fibroblast-like synoviocyte
title Low intensity pulsed ultrasound alleviates synovial fibrosis in osteoarthritis via the PI3K/AKT pathway
title_full Low intensity pulsed ultrasound alleviates synovial fibrosis in osteoarthritis via the PI3K/AKT pathway
title_fullStr Low intensity pulsed ultrasound alleviates synovial fibrosis in osteoarthritis via the PI3K/AKT pathway
title_full_unstemmed Low intensity pulsed ultrasound alleviates synovial fibrosis in osteoarthritis via the PI3K/AKT pathway
title_short Low intensity pulsed ultrasound alleviates synovial fibrosis in osteoarthritis via the PI3K/AKT pathway
title_sort low intensity pulsed ultrasound alleviates synovial fibrosis in osteoarthritis via the pi3k akt pathway
topic Osteoarthritis
Synovial fibrosis
Low-intensity pulsed ultrasound
PI3K/AKT signaling pathway
Synovitis
Fibroblast-like synoviocyte
url https://doi.org/10.1038/s41598-025-92413-x
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AT junchen lowintensitypulsedultrasoundalleviatessynovialfibrosisinosteoarthritisviathepi3kaktpathway
AT gangliu lowintensitypulsedultrasoundalleviatessynovialfibrosisinosteoarthritisviathepi3kaktpathway