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Published in: Journal of Bone and Mineral Metabolism 3/2024

04-05-2024 | Glucocorticoid | Original Article

Plasminogen activator inhibitor-1 is involved in glucocorticoid-induced decreases in angiogenesis during bone repair in mice

Authors: Kiyotaka Okada, Yuto Niwa, Kazusa Fukuhara, Takashi Ohira, Yuya Mizukami, Naoyuki Kawao, Osamu Matsuo, Hiroshi Kaji

Published in: Journal of Bone and Mineral Metabolism | Issue 3/2024

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Abstract

Introduction

Glucocorticoids delay fracture healing and induce osteoporosis. Angiogenesis plays an important role in bone repair after bone injury. Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of plasminogen activators and an adipocytokine that regulates metabolism. However, the mechanisms by which glucocorticoids delay bone repair remain unclear.

Materials and methods

Therefore, we herein investigated the roles of PAI-1 and angiogenesis in glucocorticoid-induced delays in bone repair after femoral bone injury using PAI-1-deficient female mice intraperitoneally administered dexamethasone (Dex).

Results

PAI-1 deficiency significantly attenuated Dex-induced decreases in the number of CD31-positive vessels at damaged sites 4 days after femoral bone injury in mice. PAI-1 deficiency also significantly ameliorated Dex-induced decreases in the number of CD31- and endomucin-positive type H vessels and CD31-positive- and endomucin-negative vessels at damaged sites 4 days after femoral bone injury. Moreover, PAI-1 deficiency significantly mitigated Dex-induced decreases in the expression of vascular endothelial growth factor as well as hypoxia inducible factor-1α, transforming growth factor-β1, and bone morphogenetic protein-2 at damaged sites 4 days after femoral bone injury.

Conclusion

The present results demonstrate that Dex-reduced angiogenesis at damaged sites during the early bone-repair phase after femoral bone injury partly through PAI-1 in mice.
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Metadata
Title
Plasminogen activator inhibitor-1 is involved in glucocorticoid-induced decreases in angiogenesis during bone repair in mice
Authors
Kiyotaka Okada
Yuto Niwa
Kazusa Fukuhara
Takashi Ohira
Yuya Mizukami
Naoyuki Kawao
Osamu Matsuo
Hiroshi Kaji
Publication date
04-05-2024
Publisher
Springer Nature Singapore
Published in
Journal of Bone and Mineral Metabolism / Issue 3/2024
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI
https://doi.org/10.1007/s00774-024-01510-w

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