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Shikonin promotes rat periodontal bone defect repair and osteogenic differentiation of BMSCs by p38 MAPK pathway

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Abstract

In recent years, the treatment of periodontal bone defect has been a major challenge. Cell-based bone tissue engineering provides an advanced way for bone regeneration. Bone formation hinges on the potential of osteogenesis in bone marrow stromal cells (BMSCs). Shikonin (SHI), an active principle of Radix Lithospermi, has shown a striking role to mitigate osteoporosis of ovariectomized mice, whereas its effects on periodontal bone defect are vague. Herein, we explored the impact of SHI on osteogenic differentiation of BMSCs in vitro and further analyzed the potential mechanisms using an inhibitor of p38 MAPK (SB203580). A rat periodontal bone defect model was built to assess its effects on bone formation in vivo by micro-CT and immunofluorescence. Our results showed SHI with no cytotoxicity could conspicuously enhanced alkaline phosphatase (ALP) activity, calcium accumulation and the expression of runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) of BMSCs in vitro. Increased bone volume/tissue volume (BV/TV) and osteopontin (OPN) expression after SHI administration further demonstrated the capacity of promoting osteogenesis of SHI in vivo. Furthermore, SHI could also increase the phosphorylation of p38. However, the phosphorylation of p38 and expression of osteogenic indicators promoted by SHI were reversed by SB203580, thereby illustrating the positive regulatory relationship between p38 MAPK and SHI-mediated osteogenesis. This finding may help SHI become a promising agent with respect to the therapy of periodontal bone defect.

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Data availability

All data included in this study are available upon request by contact with the corresponding author.

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Acknowledgements

Natural Science Foundation of Shandong Province (ZR2020MH182, ZR2021MH230), Clinical medicine science and technology innovation plan of **an (202019068, 2022-2-167).

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  1. **aoxin Lin and Yuxin Wang have contributed equally to this work.

Authors and Affiliations

  1. School of Stomatology, Binzhou Medical University, Yantai, 264003, Shandong, People’s Republic of China

    **aoxin Lin, Yuxin Wang, **aoli Guo, Chen Li & Siya Wang

  2. School of Stomatology, Weifang Medical University, Weifang, 261000, Shandong, People’s Republic of China

    Kuaifeng Wu

  3. Department of Endodontics, Central Laboratory of **an Stomatological Hospital, **an Key Laboratory of Oral Tissue Regeneration, **an Stomatological Hospital, **an, 250001, Shandong, People’s Republic of China

    **aoxin Lin, Yuxin Wang, **aoli Guo, Chen Li, Kuaifeng Wu, Siya Wang, **jiao Yu & Yi Du

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Lin, X., Wang, Y., Guo, X. et al. Shikonin promotes rat periodontal bone defect repair and osteogenic differentiation of BMSCs by p38 MAPK pathway. Odontology 111, 649–657 (2023). https://doi.org/10.1007/s10266-022-00774-w

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