Low‐intensity pulsed ultrasound inhibits VEGFA expression in chondrocytes and protects against cartilage degeneration in experimental osteoarthritis

Guan, Mengtong; Zhu, Ying; Liao, Bo; Tan, Qiaoyan; Qi, Han; Zhang, Bin; Huang, Junlan; Du, Xiaolan; Bai, Dingqun

doi:10.1002/2211-5463.12801

Cited by 20 publications

(17 citation statements)

References 38 publications

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“…The clinical LIPUS therapeutic system (Smith & Nephew Exogen 4000, USA) was performed. The LIPUS parameters were 30 mW/cm 2 , 1.5 MHz and 20 % duty cycle, which were consistent with the previous studies [ 13 , 14 ]. FLS were treated with TGF-β1 (10804, Sino Biological, China) at 10 ng/mL for 24 h to induce a fibrotic response [ [24] , [25] , [26] ].…”

Section: Methodssupporting

confidence: 91%

“…Furthermore, another study found that cartilage-specific ablation of mTOR could significantly reduce synovial fibrosis [ 32 ]. It has further been reported that LIPUS could regulate the function of synovial macrophages and chondrocytes in OA [ 13 , 14 , 33 ], demonstrating that the inhibition of synovial fibrosis by LIPUS may be a comprehensive effect. In OA synovial membranes, synovial macrophages produce tumor necrosis factor and IL-1β to promote the inflammatory and destructive response of FLS, as well as stimulate the proliferation of the synovium [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…6–8 weeks old C57BL/6 male mice were purchased (HuaFukang Biotechnology, Beijing, China). The DMM surgery was performed on the right knee joints, as described in our previous study [ 13 ]. 20 mice were then randomly divided into two groups, including the DMM group and the DMM + LIPUS group (n = 10, each group).…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, previous studies have found that LIPUS can alleviate joint pain and improve the quality of life in OA patients [ 12 ]. Our previous study demonstrated that LIPUS improved OA cartilage degeneration by inhibiting the secretion of vascular endothelial growth factor (VEGF) [ 13 ]. Zhang et al.…”

Section: Introductionmentioning

confidence: 99%

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

Liao

Guan

Tan

et al. 2021

Journal of Orthopaedic Translation

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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.

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Section: Methodssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Liao

Guan

Tan

et al. 2021

Journal of Orthopaedic Translation

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“…Besides, other studies demonstrated that FER1L4 promotes VEGFA expression through sequestration of miR-874-3p. VEGFA has been shown to participate in OA 22 , 23 . Targeting VEGF or its receptors to inhibit VEGF signaling showed could be a potential stand-alone or adjuvant therapy for OA 24 .…”

Section: Introductionmentioning

confidence: 99%

lncRNA FER1L4 is dysregulated in osteoarthritis and regulates IL-6 expression in human chondrocyte cells

Wang

Ding

et al. 2021

Sci Rep

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Osteoarthritis (OA) is the most prevalent joint disease and is one of the major causes of disability in the world. There has been an increase in the incidence of OA, which is associated with an aging population, sedentary lifestyle, and reduced physical activity. Due to the complex OA pathogenesis, there are limited diagnostic tools. OA is a degenerative joint disorder with a recognized inflammatory component, usually described as abnormal expression of inflammatory factors. For instance, interleukin 6 (IL‐6) has been shown to be upregulated in serum and synovial fluid among patients with OA. Most of the inflammatory factors have been associated with the expression of long noncoding RNAs (lncRNAs). However, the role of the novel lncRNA Fer-1-like protein 4 (FER1L4) in OA is yet to be determined. Here, we interrogated the expression profile of FER1L4 in patients with OA to define its potential application as a diagnostic marker. We collected synovial fluid and blood samples from both OA cases and normal controls. Using qRT-PCR, we evaluated the expression of FER1L4 in plasma and synovial fluid. On the other hand, the expression of IL-6 in plasma and synovial fluid was assessed using ELISA. Besides, the effect of age, gender or disease stage in the expression of the FER1L4 in plasma was also estimated. Moreover, the receiver operating characteristic (ROC) curves were used to determine the impact of FER1L4 in OA cases compared with the normal controls. In addition, we analyzed the correlation between FER1L4 and IL-6 through Pearson correlation analysis. Also, IL-6 expression in overexpressed FER1L4 samples was detected in chondrocytes through western blot analysis, while FER1L4 expression following endogenous IL-6 exposure was detected by qRT-PCR. Our data showed that whereas lncRNA FER1L4 is downregulated in OA patients, IL‐6 is upregulated. The plasma FER1L4 levels among the OA cases were suppressed with disease progression and old age, and the down-regulation could efficiently discriminate OA patients from normal subjects. In addition, upregulation of FER1L4 inhibited IL‐6 expression in human chondrocyte cells, and treatment with different concentrations of exogenous IL‐6 did not affect the expression of FER1L4. Taken together, our data demonstrates that FER1L4 could efficiently identify OA cases from normal subjects, and can also modulate the expression of IL‐6 in human chondrocytes.

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Low-intensity pulsed ultrasound promotes aggrecan expression via ZNT-9 in temporomandibular joint chondrocytes

Wang

et al. 2021

Gene

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Low‐intensity pulsed ultrasound inhibits VEGFA expression in chondrocytes and protects against cartilage degeneration in experimental osteoarthritis

Cited by 20 publications

References 38 publications

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

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

lncRNA FER1L4 is dysregulated in osteoarthritis and regulates IL-6 expression in human chondrocyte cells

Low-intensity pulsed ultrasound promotes aggrecan expression via ZNT-9 in temporomandibular joint chondrocytes

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