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  • Title: Intraarticular injection of dexamethasone promotes bone erosion in collagen-induced arthritis in mice through up-regulation of RANKL expression.
    Author: Sun X, Wang Y, Zhang M, Wang Q.
    Journal: Inflammopharmacology; 2019 Jun; 27(3):503-509. PubMed ID: 30343452.
    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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