Low-intensity pulsed ultrasound targeting ferroptosis to mitigate joint capsule fibrosis in a rat model of post-traumatic joint contracture
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Le résumé fourni par la source
Background: Post-traumatic joint contracture (PTJC) exhibits distinctive features such as excessive collagen deposition, which is the primary cause of joint capsule fibrosis. This work aimed to examine the therapeutic impacts and the fundamental mechanisms of low-intensity pulsed ultrasound (LIPUS) on PTJC-induced fibrosis, focusing on ferroptosis-related pathways. Methods:RNA sequencing (RNA-seq) data from the Gene Expression Omnibus (GEO) database were analyzed to identify differentially expressed genes (DEGs), followed by enrichment and correlation analyses. 40 Sprague-Dawley rats were separated into 5 groups: Sham, PTJC, Natural, LIPUS, and Combined. Rats in the LIPUS and Combined groups received LIPUS stimulation, while the Combined group also received erastin injections. Hematoxylin and Eosin (H&E) staining quantified inflammatory cell infiltration; Masson’s trichrome staining measured collagen deposition. Immunofluorescence detected Cyclin D1 (fibroblast proliferation), phosphorylated nuclear factor kappa B (p-NF-κB) p65 (inflammation), solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) (ferroptosis markers). Western blotting analyzed Collagen I/III, transforming growth factor beta 1 (TGF-β1)/Smad (fibrosis pathway). Range of motion (ROM) and joint diameter measurements evaluated contracture severity.Results:Bioinformatics analysis identified 17 ferroptosis-related and fibrosis-related target genes, withSLC7A11andGPX4selected for validation. ROM results indicated that LIPUS improved joint contracture more than the PTJC group, but the Combined group had less improvement than the LIPUS group alone. H&E and Masson’s Trichrome staining partially reversing PTJC-induced inflammation and collagen deposition. Mechanistically, immunofluorescence and Western blot indicated that LIPUS reduced fibrosis by decreasing the proliferation-related (Cyclin D1) and inflammation-related protein (p-NF-κB p65), and LIPUS inhibited PTJC-mediated initiation of TGF-β1/Smad signalling pathway and prevented inactivation of theSLC7A11/GPX4axis. Erastin counteracted LIPUS effects, confirming ferroptosis involvement.Conclusions:These findings demonstrate that LIPUS significantly mitigates PTJC-induced joint capsule fibrosis by dual mechanisms: (1) activating theSLC7A11/GPX4axis to inhibit ferroptosis and (2) suppressing TGF-β1/Smad signaling. Ferroptosis-related factors were critical as their inhibition (via erastin) exacerbated fibrosis, highlighting their role in PTJC pathogenesis.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Low-intensity pulsed ultrasound targeting ferroptosis to mitigate joint capsule fibrosis in a rat model of post-traumatic joint contracture
- Date Crossref
- 28/11/2025
- Éditeur
- Forum Multimedia Publishing LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Anhui Medical University Department of Rehabilitation Medicine pays non établi dans la noticeUniversité ou école supérieure
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First Affiliated Hospital of Anhui Medical University pays non établi dans la noticeÉtablissement de santé
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Second Affiliated Hospital of Anhui Medical University pays non établi dans la noticeÉtablissement de santé
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The People's Hospital Tongling pays non établi dans la noticeÉtablissement de santé
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First Affiliated Hospital of Bengbu Medical College pays non établi dans la noticeÉtablissement de santé
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Nepal Medical College Teaching Hospital pays non établi dans la noticeUniversité ou école supérieure
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Tongling People’s Hospital Department of Orthopedics pays non établi dans la noticeÉtablissement de santé
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The First Affiliated Hospital of Bengbu Medical University Department of Rehabilitation Medicine pays non établi dans la noticeUniversité ou école supérieure
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Bheri Hospital Department of Orthopedics pays non établi dans la noticeÉtablissement de santé
Department of Rehabilitation Medicine — Anhui Medical University, First Affiliated Hospital of Anhui Medical University et Second Affiliated Hospital of Anhui Medical University, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.