Low-intensity pulsed ultrasound inhibits fibroblast-like synoviocyte proliferation and reduces synovial fibrosis by regulating Wnt/β-catenin signaling

Bibliographic Details
Title: Low-intensity pulsed ultrasound inhibits fibroblast-like synoviocyte proliferation and reduces synovial fibrosis by regulating Wnt/β-catenin signaling
Authors: Bo Liao, Mengtong Guan, Qiaoyan Tan, Gailan Wang, Ruobin Zhang, Junlan Huang, Mi Liu, Hong Chen, Kaiting Li, Dingqun Bai, Ying Zhu
Source: Journal of Orthopaedic Translation, Vol 30, Iss , Pp 41-50 (2021)
Publisher Information: Elsevier, 2021.
Publication Year: 2021
Collection: LCC:Diseases of the musculoskeletal system
Subject Terms: Cell proliferation, Fibroblast-like synoviocyte, Low-intensity pulsed ultrasound, Osteoarthritis, Synovial fibrosis, Wnt/β-catenin signaling, Diseases of the musculoskeletal system, RC925-935
More Details: Objective: Synovial fibrosis is a characteristic symptom of osteoarthritis (OA), which is closely associated with joint pain and stiffness. Previous studies have reported that low-intensity pulsed ultrasound (LIPUS) can alleviate cartilage degradation in OA. However, the functions and mechanisms of LIPUS in OA synovial fibrosis are still unknown. Methods: The destabilization of the medial meniscus (DMM) mouse model of OA was established in C57 male mice and fibroblast-like synoviocytes (FLS) were isolated from synovial tissue of OA patients. The knee joint diameter, Masson's trichrome (MT) and Hematoxylin-eosin (HE) staining were used to evaluate synovial fibrosis and hyperplasia. The Immunohistochemistry (IHC) staining was performed to detected the expression of synovial fibrosis makers and the activation of Wnt/β-catenin signaling in vivo. FLS were treated with TGF-β1 to serve as an in vitro model of synovial fibrosis, Wnt3a was used to activate the Wnt/β-catenin signaling in cells. Cell proliferation was detected by using EdU assay, cell viability was performed by CCK8 assay. The protein levels of α-SMA, CTGF, Col Ⅰ, β-catenin, active β-catenin, c-Myc and cyclin D1 were examined by western blot and immunofluorescence staining. Results: Two weeks after the LIPUS treatment, the synovial fibrosis, synovial hyperplasia and synoviocyte proliferation in the DMM model were significantly decreased. In vitro, LIPUS directly inhibited the TGF-β1-induced fibrotic response and proliferation of FLS. Meanwhile, LIPUS suppressed Wnt/β-catenin signaling in the synovium of DMM mice and cultured FLS. More importantly, we found that the synovial fibrosis makers, Wnt/β-catenin pathway downstream proteins and FLS proliferation were significantly decreased in Wnt3a-stimulated FLS following LIPUS treatment. Conclusions: Our results present a novel role of LIPUS in OA-related synovial fibrosis, which is associated with its ability to repress Wnt/β-catenin signaling in FLS. The translational potential of this article: This study provides new insight into the clinical application of LIPUS as a therapeutic option to manage synovial fibrosis in OA.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2214-031X
Relation: http://www.sciencedirect.com/science/article/pii/S2214031X21000644; https://doaj.org/toc/2214-031X
DOI: 10.1016/j.jot.2021.08.002
Access URL: https://doaj.org/article/8b4f2b3d6b1f4ee8850ab88273c3b59e
Accession Number: edsdoj.8b4f2b3d6b1f4ee8850ab88273c3b59e
Database: Directory of Open Access Journals
More Details
ISSN:2214031X
DOI:10.1016/j.jot.2021.08.002
Published in:Journal of Orthopaedic Translation
Language:English