Xiaoxuan Sun1, Yanyan Wang1, Miaojia Zhang1, Qiang Wang2. 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. 2. Department of Rheumatology, Jiangsu Province Hospital, Nanjing Medical University First Affiliated Hospital, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People's Republic of China. jerrytortoise@163.com.
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.
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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