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Cited by 466

The DOI matches its Crossref record; 94 of the 94 references it cites were found in a registry or an index.

Exosomes from TNF-α-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss

Open access
Nakao, Yuki, Fukuda, Takao, Zhang, Qunzhou, Sanui, Terukazu, Shinjo, Takanori, Kou, Xiaoxing, Chen, Chider, Liu, Dawei, Watanabe, Yukari, Hayashi, Chikako, Yamato, Hiroaki, Yotsumoto, Karen, Tanaka, Urara, Taketomi, Takaharu, Uchiumi, Takeshi, Le, Anh D., Shi, Songtao, Nishimura, Fusanori·2021·Acta Biomaterialia
DOI 10.1016/j.actbio.2020.12.046
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Abstract

Mesenchymal stem cell (MSC)-derived exosome plays a central role in the cell-free therapeutics involving MSCs and the contents can be customized under disease-associated microenvironments. However, optimal MSC-preconditioning to enhance its therapeutic potential is largely unknown. Here, we show that preconditioning of gingival tissue-derived MSCs (GMSCs) with tumor necrosis factor-alpha (TNF-α) is ideal for the treatment of periodontitis. TNF-α stimulation not only increased the amount of exosome secreted from GMSCs, but also enhanced the exosomal expression of CD73, thereby inducing anti-inflammatory M2 macrophage polarization. The effect of GMSC-derived exosomes on inflammatory bone loss were examined by ligature-induced periodontitis model in mice. Local injection of GMSC-derived exosomes significantly reduced periodontal bone resorption and the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and these effects were further enhanced by preconditioning of GMSCs with TNF-α. Thus, GMSC-derived exosomes also exhibited anti-osteoclastogenic activity. Receptor activator of NF-κB ligand (RANKL) expression was regulated by Wnt5a in periodontal ligament cells (PDLCs), and exosomal miR-1260b was found to target Wnt5a-mediated RANKL pathway and inhibit its osteoclastogenic activity. These results indicate that significant ability of the TNF-α-preconditioned GMSC-derived exosomes to regulate inflammation and osteoclastogenesis paves the way for establishment of a therapeutic approach for periodontitis.

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Metadata

Authors
Nakao, Y., Fukuda, T., Zhang, Q., Sanui, T., Shinjo, T., Kou, X., Chen, C., Liu, D., Watanabe, Y., Hayashi, C., Yamato, H., Yotsumoto, K., Tanaka, U., Taketomi, T., Uchiumi, T., Le, A. D., Shi, S., & Nishimura, F.
Venue
Acta Biomaterialia
Publisher
Elsevier BV
Published
2021-03
Volume
122
Pages
306-324
ISSN
1742-7061 (ISSN-L)
DOI
10.1016/j.actbio.2020.12.046
OpenAlex
W3114839312
Cited by
466
References
94
FWCI
12.72
Type
journal article
Language
en
Open access
hybrid

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The paper
Nakao, Y., Fukuda, T., Zhang, Q., Sanui, T., Shinjo, T., Kou, X., Chen, C., Liu, D., Watanabe, Y., Hayashi, C., Yamato, H., Yotsumoto, K., Tanaka, U., Taketomi, T., Uchiumi, T., Le, A. D., Shi, S., & Nishimura, F. (2021). Exosomes from TNF-α-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss. Acta Biomaterialia. https://doi.org/10.1016/j.actbio.2020.12.046

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.