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Cyclosporine A Promotes Bone Remodeling in LPS-Related Inflammation via Inhibiting ROS/ERK Signaling: Studies In Vivo and In Vitro.

Abstract：

:In some inflammatory diseases of bone, osteogenesis and osteoclasis are uncoupled and the balance is usually tipped resulting in bone destruction. The underlying mechanism of osteogenic dysfunction in inflammation still needs further study. This study is aimed at investigating the effects of cyclosporine A (CsA) on bone remodeling in lipopolysaccharide- (LPS-) related inflammation. In vivo, an alveolar bone defect model was established using 10-week-old C57BL/6J mice. The mice were divided into phosphate-buffered saline (PBS), LPS, and LPS+CsA groups. After 3 weeks, micro-CT analysis and histomorphometric evaluation were conducted. In vitro, murine osteoblasts were treated with vehicle medium, LPS, LPS+CsA, LPS+extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor (LPS+PD98059), and LPS+antioxidant (LPS+EUK134). Cell proliferation, osteogenic behaviors, oxidative stress, and ERK signaling were determined. By these approaches, LPS inhibited bone remodeling and promoted oxidative stress accumulation in alveolar bone defects. When animals were treated with CsA, all LPS-induced biochemical changes ameliorated with a marked protective effect. In vitro, the reactive oxygen species (ROS) levels in mitochondria increased in LPS-treated osteoblasts, with decreased expression of osteogenic differentiation genes. The CsA, PD98059, and EUK134 presented remarkable protective effects against LPS treatment. CsA effectively enhanced bone remodeling and attenuated oxidative stress caused by LPS via inhibiting ROS/ERK signaling. Taken together, the protective effect of CsA and the inhibitory effect of ERK signaling on the maintenance of mitochondrial function and reduction of ROS levels hold promise as a potential novel therapeutic strategy for inflammatory diseases in bones.

journal_name

Oxid Med Cell Longev

journal_title

Oxidative medicine and cellular longevity

authors

Zhao Y,Gao J,Zhang Y,Gan X,Yu H

doi

10.1155/2021/8836599

subject

Has Abstract

pub_date

2021-01-07 00:00:00

pages

8836599

eissn

1942-0900

issn

1942-0994

journal_volume

2021

pub_type

杂志文章

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Cyclosporine A Promotes Bone Remodeling in LPS-Related Inflammation via Inhibiting ROS/ERK Signaling: Studies In Vivo and In Vitro.