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A Vitronectin-Derived Peptide Restores Ovariectomy-Induced Bone Loss by Dual Regulation of Bone Remodeling

  • Original Article
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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Bone remodeling is tightly regulated through bone resorption and bone formation; imbalances in bone remodeling can cause various pathological conditions such as osteoporosis. Antiresorptive agents commonly used for treating osteoporosis do not substantially reverse osteoporotic bone loss.

Methods:

We evaluated the effects of the RVYFFKGKQYWE motif (residues 270–281; VnP-16) of human vitronectin on the osteogenic differentiation of human mesenchymal stem cells (hMSCs) and osteoclastogenesis of bone marrow-derived macrophages. The effects of VnP-16 were also assessed in a mouse model of estrogen deficiency-induced osteoporosis (ovariectomized female C57BL/6 mice). To assay whether VnP-16 can reverse ovariectomy-induced bone loss, synthetic peptides or vehicle were subcutaneously injected into ovariectomized mice once a week for 4 weeks (n = 10/group). To evaluate the bone restorative effects of VnP-16, in-vivo micro-computed tomography analysis and histological staining were performed.

Results:

VnP-16 induced osteogenic differentiation of hMSCs and inhibited the RANKL–RANK–TRAF6 axis in the osteoclastogenesis signaling pathway. Furthermore, systemic administration of VnP-16 reversed ovariectomy-induced bone loss in the femoral neck, distal femur and lumbar spine by increasing osteoblast differentiation and promoting bone formation, and concomitantly decreasing osteoclastogenesis and inhibiting bone resorption. The bone restorative effect of VnP-16 was observed one week after subcutaneous administration, and although the timing of the effect differed according to bone location, it persisted for at least 3 weeks.

Conclusion:

Our findings suggest that VnP-16 is a potential therapeutic agent for treating osteoporosis that mediates its effects through dual regulation of bone remodeling.

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grants, funded by the Korean government (2016R1A2B2007246 and 2019R1F1A1054209), and the Korea Healthcare Technology R&D Project, funded by the Ministry for Health, Welfare & Family Affairs, Republic of Korea (HI15C2455).

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Author notes

  1. Hyun Ki Kang and Cho Yeon Park have been contributed equally.

Authors and Affiliations

  1. Department of Oral Biochemistry and Program in Cancer and Developmental Biology, Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehak-Ro, Jongno-Gu, Seoul, 03080, Republic of Korea

    Hyun Ki Kang, Cho Yeon Park, Sung Youn Jung, Seung Bin Jo & Byung-Moo Min

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Correspondence to Byung-Moo Min.

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Ethical statement

All procedures for obtaining human tissue specimens were reviewed and approved by the Institutional Review Board on Human Subjects Research and the Ethics Committee at Seoul National University Dental Hospital (Approval Number: CRI12004G). All animal procedures were reviewed and approved by the animal care committee of the Institute of Laboratory Animal Resources of Seoul National University (Approval Number: SNU-151104-4-2).

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Kang, H.K., Park, C.Y., Jung, S.Y. et al. A Vitronectin-Derived Peptide Restores Ovariectomy-Induced Bone Loss by Dual Regulation of Bone Remodeling. Tissue Eng Regen Med 19, 1359–1376 (2022). https://doi.org/10.1007/s13770-022-00486-w

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