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Intraarticular injection of dexamethasone promotes bone erosion in collagen-induced arthritis in mice through up-regulation of RANKL expression

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Abstract

Background

Dexamethasone (DEX) is an effective therapeutic option commonly used in the treatment of many inflammatory diseases. However, DEX could impair proliferation or differentiation of osteoblasts, suggesting a pivotal role of DEX in bone destruction.

Objective

To investigate whether intraarticular injection of DEX could exacerbate bone erosion during CIA development.

Setting

Collagen-induced arthritis (CIA) mice were divided into PBS-treated and DEX-treated groups (n = 5/group). Negative control group: DBA/1 mice (n = 5) were used as age-matched, healthy, untreated controls.

Method

CIA was induced in male DBA/1 mice. Intraarticular injected DEX (0.01 mg/Kg, 10 μl) into the knee joint of CIA on Day 28, Day 35, Day 42 and Day 49 post the 1st immunization.

Results

The severity of the arthritic disease was ameliorated in DEX-treated mice, accompanied by the decreased expression of IL-6, IL-8 and TNF-α. However, DEX treatment accelerates bone erosion and osteoporosis during CIA development and triggers higher expression of RANKL, IL-17 in vitro and vivo.

Main outcome measure

The effect of DEX on bone structure was analyzed using Haematoxylin & Eosin (H&E) staining and Micro-CT. The levels of receptor activator for nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) were investigated by real-time PCR, Western Blot and immunohistochemical analysis. RASFs were stimulated with Interleukin (IL)-1β and then treated with different concentrations of DEX for 72 h.

Conclusion

Intraarticular injection of DEX could exacerbate bone erosion in CIA model via up-regulation of RANKL expression.

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Funding

This study was supported by National Natural Science Foundation of China (NSFC) (81671615 and 81701610) and a project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and Young Medical People Project in Jiangsu Province.

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Author notes

  1. Sun Xiaoxuan and Wang Yanyan contributed equally to the work.

Authors and Affiliations

  1. Department of Rheumatology, Jiangsu Province Hospital, Nanjing Medical University First Affiliated Hospital, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People’s Republic of China

    Xiaoxuan Sun, Yanyan Wang, Miaojia Zhang & Qiang Wang

Authors
  1. Xiaoxuan Sun
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  2. Yanyan Wang
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  3. Miaojia Zhang
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  4. Qiang Wang
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Correspondence to Qiang Wang.

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The authors declare that they have no competing interests.

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Sun, X., Wang, Y., Zhang, M. et al. Intraarticular injection of dexamethasone promotes bone erosion in collagen-induced arthritis in mice through up-regulation of RANKL expression. Inflammopharmacol 27, 503–509 (2019). https://doi.org/10.1007/s10787-018-0541-6

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  • DOI: https://doi.org/10.1007/s10787-018-0541-6

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