Ibudilast mitigates delayed bone healing caused by lipopolysaccharide by altering osteoblast and osteoclast activity

Yuhan Chang, Chih Chien Hu, Ying Yu Wu, Steve W.N. Ueng, Chih Hsiang Chang*, Mei Feng Chen

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

11 引文 斯高帕斯(Scopus)

摘要

Bacterial infection in orthopedic surgery is challenging because cell wall components released after bactericidal treatment can alter osteoblast and osteoclast activity and impair fracture stability. However, the precise effects and mechanisms whereby cell wall components impair bone healing are unclear. In this study, we characterized the effects of lipopolysaccharide (LPS) on bone healing and osteoclast and osteoblast activity in vitro and in vivo and evaluated the effects of ibudilast, an antagonist of toll-like receptor 4 (TLR4), on LPS-induced changes. In particular, microcomputed tomography was used to reconstruct femoral morphology and analyze callus bone content in a femoral defect mouse model. In the sham-treated group, significant bone bridge and cancellous bone formation were observed after surgery, however, LPS treatment delayed bone bridge and cancellous bone formation. LPS inhibited osteogenic factor-induced MC3T3-E1 cell differentiation, alkaline phosphatase (ALP) levels, calcium deposition, and osteopontin secretion and increased the activity of osteoclast-associated molecules, including cathepsin K and tartrate-resistant acid phosphatase in vitro. Finally, ibudilast blocked the LPS-induced inhibition of osteoblast activation and activation of osteoclast in vitro and attenuated LPS-induced delayed callus bone formation in vivo. Our results provide a basis for the development of a novel strategy for the treatment of bone infection.

原文英語
文章編號1169
頁(從 - 到)1-10
頁數10
期刊International Journal of Molecular Sciences
22
發行號3
DOIs
出版狀態已出版 - 01 02 2021

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© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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