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Possible reparative effect of low-intensity pulsed ultrasound (LIPUS) on injured meniscus

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Journal of Cell Communication and Signaling Aims and scope

Abstract

Menisci are a pair of crescent-shaped fibrocartilages, particularly of which their inner region of meniscus is an avascular tissue. It has characteristics similar to those of articular cartilage, and hence is inferior in healing. We previously reported that low-intensity pulsed ultrasound (LIPUS) treatment stimulates the production of CCN2/CTGF, a protein involved in repairing articular cartilage, and the gene expression of major cartilage matrices such as type II collagen and aggrecan in cultured chondrocytes. Therefore, in this present study, we investigated whether LIPUS has also favorable effect on meniscus cells and tissues. LIPUS applied with a 60 mW/cm2 intensity for 20 min stimulated the gene expression and protein production of CCN2 via ERK and p38 signaling pathways, as well as gene expression of SOX9, aggrecan, and collagen type II in human inner meniscus cells in culture, and slightly stimulated the gene expression of CCN2 and promoted the migration in human outer meniscus cells in culture. LIPUS also induced the expression of Ccn2, Sox9, Col2a1, and Vegf in rat intact meniscus. Furthermore, histological evaluations showed that LIPUS treatment for 1 to 4 weeks promoted healing of rat injured lateral meniscus, as evidenced by better and earlier angiogenesis and extracellular matrix synthesis. The data presented indicate that LIPUS treatment might prevent meniscus from degenerative change and exert a reparative effect on injured meniscus via up-regulation of repairing factors such as CCN2 and that it might thus be useful for treatment of an injured meniscus as a non-invasive therapy.

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Abbreviations

CCN:

Cysteine-rich 61, Connective tissue growth factor, Nephroblastoma-overexpressed

CCN2:

CCN family member 2, Connective tissue growth factor

CCN3:

CCN family member 3, Nephroblastoma-overexpressed

DMEM:

Dulbecco’s modified Eagle’s medium

ECM:

Extracellular matrix

FBS:

Fetal bovine serum

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

LIPUS:

Low-intensity pulsed ultrasound

OA:

Osteoarthritis

PAGE:

Polyacrylamide gel electrophoresis

PDGF:

Platelet-derived growth factor

PVDF:

Polyvinylidene difluoride

PRP:

Platelet-rich plasma

LM:

Lateral meniscus

siRNA:

Small interfering RNA

SOX9:

Sry-type high-mobility-group box 9

TKA:

Total knee arthroplasty

TGF-β:

Transforming growth factor-beta

VEGF:

Vascular endothelial growth factor

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Acknowledgments

We thank Ms. Yoshiko Miyake for her secretarial assistance. We also thank Masataka Fujii, Yuya Kodama, Tomohito Hino, Yoshiki Okazaki, Shin Masuda and Yuki Okazaki for their clinical supports.

Funding

This work was supported in part by grants from the programs Grants-in-Aid for Scientific Research (B) to MT (#JP15H05014), and for Challenging Exploratory Research to MT (#JP17K19757) from Japan Society for the Promotion of Sciences, Japan.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kitaku, Okayama, 700-8558, Japan

    Yusuke Kamatsuki, Takayuki Furumatsu & Toshifumi Ozaki

  2. Advanced Research Center for Oral and Craniofacial Sciences (ARCOCS), Okayama University Dental School/Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan

    Yusuke Kamatsuki, Eriko Aoyama, Satoshi Kubota & Masaharu Takigawa

  3. Department of Intelligent Orthopedic System, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, Japan

    Shinichi Miyazawa & Ami Maehara

  4. ITO Co., Ltd., 3-1-8 Sakae-cho, Kawaguchi, Saitama, 332-0017, Japan

    Nobuyasu Yamanaka

  5. Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan

    Takashi Nishida & Satoshi Kubota

Authors
  1. Yusuke Kamatsuki
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  2. Eriko Aoyama
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  3. Takayuki Furumatsu
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  4. Shinichi Miyazawa
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  5. Ami Maehara
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  6. Nobuyasu Yamanaka
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  7. Takashi Nishida
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  8. Satoshi Kubota
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  9. Toshifumi Ozaki
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  10. Masaharu Takigawa
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Corresponding author

Correspondence to Masaharu Takigawa.

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Conflict of interest

NY is a managing director of Ito Co., Ltd.. and MT received research funding from this company. SM’s salary is supported by Teijin Nakashima Medical Co. Ltd. All other authors state that they have no conflicts of interest.

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This article does not contain any studies using human participants.

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Kamatsuki, Y., Aoyama, E., Furumatsu, T. et al. Possible reparative effect of low-intensity pulsed ultrasound (LIPUS) on injured meniscus. J. Cell Commun. Signal. 13, 193–207 (2019). https://doi.org/10.1007/s12079-018-0496-9

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  • DOI: https://doi.org/10.1007/s12079-018-0496-9

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