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Adipose Tissue-Derived Mesenchymal Stem Cell Inhibits Osteoclast Differentiation through Tumor Necrosis Factor Stimulated Gene-6

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Mesenchymal stem cells (MSCs) have been highlighted as a potent therapeutic option for conditions with excessive osteoclast activity such as systemic and local bone loss in rheumatic disease. In addition to their immunomodulatory functions, MSCs also directly suppress osteoclast differentiation and activation by secreting osteoprotegerin (OPG) and IL-10 but the underlying mechanisms are still to be clarified. Tumor necrosis factor-stimulated gene-6 (TSG-6) is a potent anti-inflammatory molecule that inhibits osteoclast activation and has been shown to mediate MSC’s immunomodulatory functions. In this study, we aimed to determine whether adipose tissue-derived MSC (ADMSC) inhibits the differentiation from osteoclast precursors to mature osteoclasts through TSG-6.

Methods:

Human ADMSCs were co-cultured with bone marrow-derived monocyte/macrophage (BMMs) from DBA/1J or B6 mouse in the presence of osteoclastogenic condition (M-CSF 10 ng/mL and RANKL 10 ng/mL). In some co-culture groups, ADMSCs were transfected with siRNA targeting TSG-6 or OPG to determine their role in osteoclastogenesis. Tartrate-resistant acid phosphatase (TRAP) activity in culture supernatant and mRNA expression of osteoclast markers were investigated. TRAP+ multinucleated cells and F-actin ring formation were counted.

Results:

ADMSCs significantly inhibited osteoclast differentiation under osteoclastogenic conditions. Suppression of TSG-6 significantly reversed the inhibition of osteoclast differentiation in a degree similar to that of OPG based on TRAP activity, mRNA expression of osteoclast markers, and numbers of TRAP+ multinucleated cell and F-actin ring formation.

Conclusion:

This study demonstrated that ADMSCs inhibit osteoclast differentiation through TSG-6 under osteoclastogenic conditions.

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Data availability statement

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was supported by Dongguk University Research Fund of 2022, Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2018R1D1A1B07050276), Severance Hospital,Yonsei University Health System (4-2021-0599) and the Korean Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (HI14C1324).

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea

    Kwanghoon Lee, Eunhee Ko & Yongbeom Park

  2. Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea

    Eunhee Ko & Yongbeom Park

  3. Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea

    Yongbeom Park

  4. Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, 10326, Republic of Korea

    Kwanghoon Lee

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  1. Kwanghoon Lee
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Correspondence to Yongbeom Park.

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Ethical statement

All animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Yonsei University Health System (approval number: 2020 − 0291).

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Supplementary figure 1

Efficacy of siRNA transfection (TSG-6). ADMSCs were transfected with siRNA targeting TSG-6 according to manufacturer’s instructions. Compared to the ADMSCS of no siRNA transfection (No transf.) and scramble siRNA transfection (Scr. siRNA), TSG-6 mRNA suppression was apparent in ADMSCs transfected with siRNA targeting TSG-6 as early as 10 hours after transfection and was maintained through 24 hours after (JPG 42.7 kb)

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Lee, K., Ko, E. & Park, Y. Adipose Tissue-Derived Mesenchymal Stem Cell Inhibits Osteoclast Differentiation through Tumor Necrosis Factor Stimulated Gene-6. Tissue Eng Regen Med 21, 587–594 (2024). https://doi.org/10.1007/s13770-023-00619-9

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  • DOI: https://doi.org/10.1007/s13770-023-00619-9

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