Dexamethasone, as one member of the glucocorticoid family, can protect against arthritis-related changes in cartilage structure and function, including matrix loss, inflammation and cartilage viability. [1]
In vitro, treatment with 10 nM to 1 μM dexamethasone by 96 h increased the CPPD crystal depositionin in porcine chondrocytes.[5] In vitro experiment it indicated that GR mediates OATP2B1 downregulation induced by dexamethasone (500 nM) in placental trophoblast cells, while farnesoid X receptor mediates BCRP downregulation and MRP4 upregulation.[6] In addition, administration of 25 nM dexamethasone in isolated myogenic satellite cells results in the greatest increase in committed myogenic progenitors. And differentiation of myoblasts into myotubes was greatest with treatment of 25 nM dexamethasone at early differentiation for 5–7days and sustained treatment of 10 nM dexamethasone for 0–7 days.[7]
In vivo, treatment with 2.5 mg/kg/day orally in mice significantly increased the percent of CTLA-4-expressing CD8 T cells.[2] In vivo experiment it shown that collagen-induced mouse was daily intravenously injected of free 1.6 mg/kg Dexamethasone or a single injected of 0.4–4 mg/kg liposomalencapsulated Dexamethasone, the frequency of arthritis occurrence and lower its severity reduced. [3] With 0.1 mg/kg dexamethasone starting 11 d after surgery decrease animal pain response in the affected paw, lowers inflammation and macrophage infiltration and partially rescues PG loss in the joint cartilage in a rat meniscal transection OA model.[4]
地塞米松是糖皮质激素家族的一员，可以保护软骨结构和功能免受关节炎相关变化的影响，包括基质丢失、炎症和软骨活力。[1]
在离体实验中，96小时内使用10 nM至1 μM的地塞米松治疗增加了猪软骨细胞中CPPD晶体沉积。[5] 离体实验表明，在500 nM的地塞米松诱导下，GR介导了胎盘滋养层细胞中OATP2B1的下调，而法尼酸X受体介导BCRP的下调和MRP4的上调。[6] 此外，在分离的肌肉卫星细胞中给予25 nM地塞米松可使承诺性肌源祖细胞数量最大。并且，在早期分化时连续治疗0-7天10 nM地塞米松以及在5-7天时用25 nM地塞米松处理可以使成肌母细胞向肌管转化程度最高。[7]
在小鼠体内，口服每日2.5毫克/千克的治疗显著增加了表达CTLA-4的CD8 T细胞的百分比。在小鼠诱导胶原病实验中，每天静脉注射1.6毫克/千克自由地塞米松或单次注射0.4-4毫克/千克脂质体包埋地塞米松可以降低关节炎发生频率和减轻其严重程度。使用0.1毫克/千克地塞米松开始于手术后第11天，在大鼠半月板切除OA模型中降低动物对受影响爪子的疼痛反应，减少了炎症和巨噬细胞浸润，并部分挽救了关节软骨中PG损失。
参考文献:
[1] Black R, et al. Dexamethasone: chondroprotective corticosteroid or catabolic killer? Eur Cell Mater. 2019 Nov 22;38:246-263.
[2] Giles AJ, et al. Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy. J Immunother Cancer. 2018 Jun 11;6(1):51.?
[3] Rauchhaus U, et al. Separating therapeutic efficacy from glucocorticoid side-effects in rodent arthritis using novel, liposomal delivery of dexamethasone phosphate: long-term suppression of arthritis facilitates interval treatment. Arthritis Res Ther. 2009;11(6):R190.?
[4] Ashraf S, et al. Contributions of angiogenesis to inflammation, joint damage, and pain in a rat model of osteoarthritis. Arthritis Rheum. 2011 Sep;63(9):2700-10.
[5] Fahey M, et al. Dexamethasone promotes calcium pyrophosphate dihydrate crystal formation by articular chondrocytes. J Rheumatol. 2009 Jan;36(1):163-9.
[6] Huang W, et al. Dexamethasone induces an imbalanced fetal-placental-maternal bile acid circulation: involvement of placental transporters. BMC Med. 2021 Apr 7;19(1):87.
[7] Larson AA, et al. Effects of Dexamethasone Dose and Timing on Tissue-Engineered Skeletal Muscle Units. Cells Tissues Organs. 2018;205(4):197-207.
| Cell experiment [1]: | |
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Cell lines |
The human choriocarcinoma cell line BeWo |
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Preparation Method |
Treated BeWo with 20, 100, and 500?nM of dexamethasone for 5 days, respectively. Cells were cultured in 96-well plates in the presence of dexamethasone at different concentrations (0, 20, 100, and 500?nM) for 5 days. MTS assay was conducted to detect the cytotoxicity of dexamethasone on BeWo cells following the manufacturer’s protocol. |
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Reaction Conditions |
0, 20, 100, and 500?nM, 5 days |
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Applications |
Dexamethasone decreased OATP2B1 and BCRP mRNA expression and increased the MRP4 mRNA expression in a concentration-dependent manner. |
| Animal experiment [2]: | |
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Animal models |
Six to eight week-old female albino C57BL/6 mice |
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Preparation Method |
For intracranial tumor implantation, mice were injected with 1x 103 GL261 cells that were stably transduced with a firefly luciferase-mCherry lentiviral vector. Water-soluble dexamethasone was administered at 1 mg/kg/day by oral gavage. |
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Dosage form |
1 mg/kg/day，oral gavage |
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Applications |
Dexamethasone increased the percentage of CTLA-4-expressing CD4 T cells of tumor-bearing mice in a dose-dependent manner. CTLA-4 blockade enhances survival of dexamethasone-treated mice. |
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参考文献: [1]. Huang W, et al. Dexamethasone induces an imbalanced fetal-placental-maternal bile acid circulation: involvement of placental transporters. BMC Med. 2021 Apr 7;19(1):87. [2]. Giles AJ, et al. Dexamethasone-induced immunosuppression: mechanisms and implications for immunotherapy. J Immunother Cancer. 2018 Jun 11;6(1):51.? |
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