Inhibitory effect of hydroxychloroquine on glucocorticoid-induced osteoporosis in lupus therapy

IF 4.6 2区 医学 Q2 IMMUNOLOGY Clinical & Translational Immunology Pub Date : 2024-10-14 DOI:10.1002/cti2.70010
Wenlin Qiu, Xiaoxiao Han, Tong Yu, Lijuan Jiang, Xuefei Wang, Ruizhi Feng, Xiaoru Duan, Yao Teng, Haifeng Yin, Maria I Bokarewa, Guo-Min Deng
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Abstract

Objectives

Systemic lupus erythematosus (SLE) is a chronic and severe autoimmune disease characterised by persistent inflammation. Hydroxychloroquine (HCQ) and glucocorticoids (GCs) are the primary agents commonly used in combination as the first-line treatment for SLE. Nevertheless, the specific mechanisms responsible for the effectiveness of this combined therapy with HCQ and GCs have not been fully elucidated. This study aimed to reveal the mechanism behind combined HCQ and GC treatment in lupus.

Methods

An SLE IgG-induced inflammation model was used to investigate the anti-inflammatory effects of HCQ and dexamethasone (DXM). A glucocorticoid-induced osteoporosis (GIOP) model was used to investigate the inhibitory effect of HCQ on osteoclastogenesis. Inflammation was assessed by haematoxylin and eosin staining. Bone metabolism was determined structurally via microcomputer tomography and in bone marrow-derived osteoclast cultures.

Results

An SLE IgG-induced inflammation model demonstrated that HCQ could not ameliorate inflammation alone but could enhance the anti-inflammatory effect of GCs by decreasing the expression of FcγRI on macrophages. HCQ inhibited osteoclastogenesis induced by GCs and RANKL by upregulating nuclear factor erythroid 2-related factor 2 and limiting reactive oxygen species formation, which mitigated GC-induced bone loss.

Conclusion

The results indicate that HCQ improved the anti-inflammatory effects of GCs and inhibits the osteoclastogenesis in experimental lupus. This study offers valuable insights into the mechanisms underlying the combined treatment of lupus with HCQ and GCs.

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羟氯喹对红斑狼疮治疗中糖皮质激素诱导的骨质疏松症的抑制作用
目的 系统性红斑狼疮(SLE)是一种以持续炎症为特征的慢性严重自身免疫性疾病。羟氯喹(HCQ)和糖皮质激素(GCs)是系统性红斑狼疮一线治疗常用的主要药物。然而,羟氯喹和糖皮质激素联合治疗有效的具体机制尚未完全阐明。本研究旨在揭示HCQ和GCs联合治疗狼疮的机制。 方法 采用系统性红斑狼疮 IgG 诱导的炎症模型来研究 HCQ 和地塞米松(DXM)的抗炎作用。糖皮质激素诱导的骨质疏松症(GIOP)模型用于研究 HCQ 对破骨细胞生成的抑制作用。炎症通过血红素和伊红染色进行评估。通过微计算机断层扫描和骨髓破骨细胞培养从结构上测定骨代谢。 结果 系统性红斑狼疮 IgG 诱导的炎症模型表明,HCQ 不能单独改善炎症,但能通过降低巨噬细胞上 FcγRI 的表达增强 GCs 的抗炎作用。HCQ 通过上调核因子红细胞 2 相关因子 2 和限制活性氧的形成,抑制了 GCs 和 RANKL 诱导的破骨细胞生成,从而减轻了 GC 诱导的骨质流失。 结论 研究结果表明,HCQ 可改善 GCs 的抗炎作用并抑制实验性狼疮的破骨细胞生成。这项研究为了解 HCQ 和 GCs 联合治疗红斑狼疮的机制提供了宝贵的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical & Translational Immunology
Clinical & Translational Immunology Medicine-Immunology and Allergy
CiteScore
12.00
自引率
1.70%
发文量
77
审稿时长
13 weeks
期刊介绍: Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.
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