Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Zhao, Xiang; Zhao, Gang-Sheng; Shi, Zhijun; Zhou, Chenhe; Chen, Yunlin; Hu, Bin; Yan, Shigui

doi:10.1038/srep45779

Cited by 16 publications

(18 citation statements)

References 38 publications

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“…We previously reported to this extent that LIPUS stimulation inhibits Toll‐like receptor 4‐myeloid differentiation primary response gene 88 (MyD88) complex formation . Other reports have also shown that LIPUS downregulates the protein expression levels of IL‐1β receptor, and TNF receptor associated factor 6 . In the present study, we found that ROCK1, a molecule majorly involved in cytoskeletal rearrangements following activation by Rho, was critically involved in the suppressive effects of LIPUS on inflammatory reactions (Figure ).…”

Section: Discussionsupporting

confidence: 68%

Low‐intensity pulsed ultrasound promotes bone morphogenic protein 9‐induced osteogenesis and suppresses inhibitory effects of inflammatory cytokines on cellular responses via Rho‐associated kinase 1 in human periodontal ligament fibroblasts

Kusuyama

Nakamura

Ohnishi

et al. 2019

J of Cellular Biochemistry

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Periodontal ligament fibroblasts (PDLFs) have osteogenic capacity, producing bone matrix proteins. Application of bone morphogenic proteins (BMPs) to PDLFs is a promising approach for periodontal regeneration. However, in chronic bone metabolic disorders, such as periodontitis, proper control of accompanying inflammation is essential for optimizing the effects of BMPs on PDLFs. We have previously shown that low‐intensity pulsed ultrasound (LIPUS), a medical technology that induces mechanical stress using sound waves, significantly promotes osteogenesis in mesenchymal stem cells. Here, we demonstrate that LIPUS promotes the BMP9‐induced osteogenic differentiation of PDLFs. In contrast, BMP2‐induced osteogenic differentiation was not altered by LIPUS, probably due to the LIPUS‐induced secretion of Noggin, a BMP2 antagonist, from PDLFs. To examine if LIPUS affects inflammatory responses of PDLFs to lipopolysaccharide (LPS) derived from Porphyromonas gingivalis (LPS‐PG), we also simultaneously treated PDLFs with LIPUS and LPS‐PG. Treatment with LIPUS significantly inhibited the phosphorylation of ERKs, TANK‐binding kinase 1, and interferon regulatory factor 3 in LPS‐PG‐stimulated PDLFs, in addition to inhibiting the degradation of IκB. Furthermore, LIPUS treatment reduced messenger RNA (mRNA) expression of interleukin‐1alpha (IL‐1alpha), IL‐1beta, IL‐6, IL‐8, C‐C motif chemokine ligand 2, C‐X‐C motif chemokine ligand 1 (CXCL1), CXCL10 and receptor activator of nuclear factor kappa‐B ligand, and also diminished IL‐1ß and tumor necrosis factor a (TNFa)‐induced inflammatory reactions. Phosphorylation of Rho‐associated kinase 1 (ROCK1) was induced by LIPUS, while ROCK1‐specific inhibitor prevented the promotive effects of LIPUS on p38 phosphorylation, mRNA expression of CXCL1 and Noggin, and osteogenesis. The suppressive effects of LIPUS on LPS‐PG‐stimulated inflammatory reactions were also prevented by ROCK1 inhibition. Moreover, LIPUS treatment blocked inhibitory effects of LPS‐PG and IL‐1ß on osteogenesis. These results indicate that LIPUS suppresses inflammatory effects of LPS‐PG, IL‐1ß, and TNFa and also promotes BMP9‐induced osteogenesis through ROCK1 in PDLFs.

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Section: Discussionsupporting

confidence: 68%

Low‐intensity pulsed ultrasound promotes bone morphogenic protein 9‐induced osteogenesis and suppresses inhibitory effects of inflammatory cytokines on cellular responses via Rho‐associated kinase 1 in human periodontal ligament fibroblasts

Kusuyama

Nakamura

Ohnishi

et al. 2019

J of Cellular Biochemistry

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“…The number of regenerated axons, the mean diameter of the regenerated axons, and the thickness of the myelin sheath on these axons were all significantly different from the corresponding values in SN-SC group. Additionally, Masson's trichrome staining and electrophysiological analyses are widely accepted techniques for functionally evaluating sciatic nerve repair 41 , 42 . The results obtained in the Fb&SC group were preferable to those obtained in the SN-SC group with regard for functional recovery.…”

Section: Discussionmentioning

confidence: 99%

The effect of co-transplantation of nerve fibroblasts and Schwann cells on peripheral nerve repair

Wang¹,

Liu²,

Wang³

et al. 2017

Int. J. Biol. Sci.

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Combinations of fibroblasts (Fbs) and corresponding epithelial cells have been widely used in many tissues, such as the skin and breast tissues, to augment tissue repair and remodeling. Recently, a large amount of new data has indicated that nerve Fbs play critical roles in Schwann cells (SCs) and axons in vitro. However, little is known regarding the effects of co-transplanting nerve Fbs and SCs on peripheral nerve repair in vivo. The aim of this study was to investigate the effect of co-transplanting sciatic nerve Fbs (SN-Fbs) and sciatic nerve SCs (SN-SCs) on nerve regeneration. We developed a 5 mm nerve-defect model in mice using a polyurethane (PUR) catheter and then injected one of four different mixtures of cells into the catheters to form the following four groups: pure Matrigel (Control group), SN-Fbs alone (SN-Fb group), SN-Fbs combined with SN-SCs at a ratio of 1:2 (Fb&SC group) and SN-SCs alone (SN-SC group). Histological and functional analyses were performed 3 months later. The results indicated that in vitro, the expression levels of NGF, BDNF and GDNF were significantly higher, and in vivo, a more moderate amount of extracellular matrix was produced in the Fb&SC group than in the SN-SC group. Compared to the other groups, co-transplanting SN-Fbs with SCs at a 1:2 ratio had significantly positive effects on nerve regeneration and functional recovery.

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“…LIPUS has been recently reported to have biologic relevance in the context of inflammation. LIPUS treatment was shown to alleviate the lipopolysaccharide-induced inflammatory response in murine RAW264.7 macrophages by increasing the activation of caveolin-1 [ 95 ], and also improved the general status of coxsackievirus-B3-infected mice including their ventricular function by suppressing CD68+ infiltration in the heart [ 96 , 97 ]. Related to inflammation, LIPUS was found to inhibit the inflammatory pathways activated during aseptic joint loosening [ 97 ], suggesting an anti-inflammatory role for LIPUS in the orthopedic context.…”

Section: Biological Effects Of Ultrasoundmentioning

confidence: 99%

“…LIPUS treatment was shown to alleviate the lipopolysaccharide-induced inflammatory response in murine RAW264.7 macrophages by increasing the activation of caveolin-1 [ 95 ], and also improved the general status of coxsackievirus-B3-infected mice including their ventricular function by suppressing CD68+ infiltration in the heart [ 96 , 97 ]. Related to inflammation, LIPUS was found to inhibit the inflammatory pathways activated during aseptic joint loosening [ 97 ], suggesting an anti-inflammatory role for LIPUS in the orthopedic context. In a similar line, LIPUS was shown to inhibit the production of mature IL1β in a murine model of synovial inflammation [ 98 ], and to reduce histological damage and lesion size in the joints of mice with systemic autoimmunity [ 99 ].…”

Section: Biological Effects Of Ultrasoundmentioning

confidence: 99%

Ultrasound Therapy: Experiences and Perspectives for Regenerative Medicine

Lucas

Pérez

Bernal

et al. 2020

Genes

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Ultrasound has emerged as a novel tool for clinical applications, particularly in the context of regenerative medicine. Due to its unique physico-mechanical properties, low-intensity ultrasound (LIUS) has been approved for accelerated fracture healing and for the treatment of established non-union, but its utility has extended beyond tissue engineering to other fields, including cell regeneration. Cells and tissues respond to acoustic ultrasound by switching on genetic repair circuits, triggering a cascade of molecular signals that promote cell proliferation, adhesion, migration, differentiation, and extracellular matrix production. LIUS also induces angiogenesis and tissue regeneration and has anti-inflammatory and anti-degenerative effects. Accordingly, the potential application of ultrasound for tissue repair/regeneration has been tested in several studies as a stand-alone treatment and, more recently, as an adjunct to cell-based therapies. For example, ultrasound has been proposed to improve stem cell homing to target tissues due to its ability to create a transitional and local gradient of cytokines and chemokines. In this review, we provide an overview of the many applications of ultrasound in clinical medicine, with a focus on its value as an adjunct to cell-based interventions. Finally, we discuss the various preclinical and clinical studies that have investigated the potential of ultrasound for regenerative medicine.

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Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway

Cited by 16 publications

References 38 publications

Low‐intensity pulsed ultrasound promotes bone morphogenic protein 9‐induced osteogenesis and suppresses inhibitory effects of inflammatory cytokines on cellular responses via Rho‐associated kinase 1 in human periodontal ligament fibroblasts

Low‐intensity pulsed ultrasound promotes bone morphogenic protein 9‐induced osteogenesis and suppresses inhibitory effects of inflammatory cytokines on cellular responses via Rho‐associated kinase 1 in human periodontal ligament fibroblasts

The effect of co-transplantation of nerve fibroblasts and Schwann cells on peripheral nerve repair

Ultrasound Therapy: Experiences and Perspectives for Regenerative Medicine

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