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Exosomes derived from human exfoliated deciduous teeth ameliorate adult bone loss in mice through promoting osteogenesis

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Abstract

Cell-free based therapy is an effective strategy in regenerative medicine as it avoids controversial issues, such as immunomodulation and stability. Recently, exosomes have been explored as a favorable substitution for stem cell therapy as they exhibit multiple advantages, such as the ability to be endocytosed and innate biocompatibility. This study aimed to investigate the effects of stem cells from human exfoliated deciduous teeth (SHED)-derived exosomes (SHED-Exo) on bone marrow stromal cells (BMSCs) osteogenesis and bone recovery. SHED-Exo were isolated, characterized, and applied to the bone loss area caused by periodontitis in a mouse model. We found that the injection of SHED-Exo restored bone loss to the same extent as original stem cells. Without affecting BMSCs proliferation, SHED-Exo mildly inhibited apoptosis. Moreover, SHED-Exo specifically promoted BMSCs osteogenesis and inhibited adipogenesis compared with SHED-derived conditioned medium. The expression of osteogenic marker genes, alkaline phosphatase activity, and Alizarin Red S staining of BMSCs was significantly increased by co-culturing with SHED-Exo. Moreover, Western blot analysis showed that Runx2, a key transcriptional factor in osteogenic differentiation, and p-Smad5 were upregulated upon SHED-Exo stimulation. Expression of the adipogenic marker PPARγ and the amount of lipid droplets decreased when exosomes were present. Low doses of exosomes inhibited the expression of the inflammatory cytokines IL-6 and TNF-α. In conclusion, SHED-Exo directly promoted BMSCs osteogenesis, differentiation, and bone formation. Therefore, exosomes have the potential to be utilized in the treatment of periodontitis and other bone diseases.

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Data availability

The authors declare that the data supporting the findings of this study are available within the manuscript and the supplementary materials.

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Funding

This study was financially supported by grants from the National Natural Science Foundation of China Nos. 81970901(N.J), 81600820(N.J) and 81801014 (Y.Z).

Author information

Authors and Affiliations

  1. Department of Periodontics, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China

    Jizhen Wei & Xuejun Ge

  2. Central Laboratory, Peking University School and Hospital of Stomatology, #22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China

    Jizhen Wei, Yeqing Song, Zhihao Du & Nan Jiang

  3. Department of Oral Medicine, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, China

    Feiyan Yu

  4. First Dental Center, Peking University School and Hospital of Stomatology, Beijing, China

    Yimei Zhang

Authors
  1. Jizhen Wei
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  2. Yeqing Song
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  7. Xuejun Ge
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Contributions

JW contributed to study design, data collection, statistical analysis and data interpretation; YS and ZD contributed to data collection and data interpretation; FY contributed to literature search; YZ contributed to exosomes collection and data collection and fund collection; NJ contributed to manuscript preparation and funds collection. NJ and XG contributed to study design, statistical analysis, data interpretation and manuscript revision. All authors approved the final version of the manuscript.

Corresponding authors

Correspondence to Nan Jiang or Xuejun Ge.

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Protocols were approved by the Peking University Ethical Committee (LA2019148).

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10735_2020_9896_MOESM1_ESM.tif

Supplementary Fig. 1 a–d Representative immunohistochemistry staining of TNF-α in periodontal defect areas after periodontitis establishment (Perio), and the following treatments for 2 weeks. Supplementary file1 (TIF 6131 kb)

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Wei, J., Song, Y., Du, Z. et al. Exosomes derived from human exfoliated deciduous teeth ameliorate adult bone loss in mice through promoting osteogenesis. J Mol Hist 51, 455–466 (2020). https://doi.org/10.1007/s10735-020-09896-3

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  • DOI: https://doi.org/10.1007/s10735-020-09896-3

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