DEXAMETHASONE: CHONDROPROTECTIVE CORTICOSTEROID OR CATABOLIC KILLER?
DEXAMETHASONE: CHONDROPROTECTIVE CORTICOSTEROID OR CATABOLIC KILLER?
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DOI：
10.22203/ecm.v038a17
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发表时间：
2019-07-01
影响因子：
3.1
通讯作者：
Grodzinsky, A. J.
中科院分区：
文献类型：
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作者：
Black, R.;Grodzinsky, A. J.
虽然糖皮质激素用于治疗类风湿和骨关节炎疼痛已有50多年的历史，但由于在分子、细胞和组织水平上存在潜在的有害副作用，糖皮质激素的处方仍然存在争议。地塞米松（dexamethasone， DEX）是糖皮质激素家族的一员，最近在动物研究和组织损伤和创伤后骨关节炎的软骨移植模型中被证明可以挽救软骨基质丧失和软骨细胞活力，这表明如果使用得当，地塞米松有可能成为一种疾病改善药物。然而，关于DEX对软骨影响的文献揭示了药物安全性的相互矛盾的结果，这取决于DEX暴露的剂量和持续时间以及所使用的模型系统。总的来说，DEX已被证明可以防止关节炎相关的软骨结构和功能变化，包括基质损失、炎症和软骨活力。这些有益的影响并不总是在使用最初健康的软骨或分离的软骨细胞的模型系统中观察到，许多研究已经报道了软骨细胞凋亡的显著增加。至关重要的是要了解在什么条件下DEX可能对软骨和其他关节组织有益或有害，并确定这种糖皮质激素在临床中作为一种疾病缓解药物的安全使用潜力。
While glucocorticoids have been used for over 50 years to treat rheumatoid and osteoarthritis pain, the prescription of glucocorticoids remains controversial because of potentially harmful side effects at the molecular, cellular and tissue levels. One member of the glucocorticoid family, dexamethasone (DEX) has recently been demonstrated to rescue cartilage matrix loss and chondrocyte viability in animal studies and cartilage explant models of tissue injury and post-traumatic osteoarthritis, suggesting the possibility of DEX as a disease-modifying drug if used appropriately. However, the literature on the effects of DEX on cartilage reveals conflicting results on the drug's safety, depending on the dose and duration of DEX exposure as well as the model system used. Overall, DEX has been shown to protect against arthritis-related changes in cartilage structure and function, including matrix loss, inflammation and cartilage viability. These beneficial effects are not always observed in model systems using initially healthy cartilage or isolated chondrocytes, where many studies have reported significant increases in chondrocyte apoptosis. It is crucially important to understand under what conditions DEX may be beneficial or harmful to cartilage and other joint tissues and to determine potential for safe use of this glucocorticoid in the clinic as a disease-modifying drug.