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Arthritis and the role of endogenous glucocorticoids.
Bone Research ( IF 14.3 ) Pub Date : 2020-09-08 , DOI: 10.1038/s41413-020-00112-2
Eugenie Macfarlane 1 , Markus J Seibel 1 , Hong Zhou 1
Affiliation  

Rheumatoid arthritis and osteoarthritis, the most common forms of arthritis, are chronic, painful, and disabling conditions. Although both diseases differ in etiology, they manifest in progressive joint destruction characterized by pathological changes in the articular cartilage, bone, and synovium. While the potent anti-inflammatory properties of therapeutic (i.e., exogenous) glucocorticoids have been heavily researched and are widely used in clinical practice, the role of endogenous glucocorticoids in arthritis susceptibility and disease progression remains poorly understood. Current evidence from mouse models suggests that local endogenous glucocorticoid signaling is upregulated by the pro-inflammatory microenvironment in rheumatoid arthritis and by aging-related mechanisms in osteoarthritis. Furthermore, these models indicate that endogenous glucocorticoid signaling in macrophages, mast cells, and chondrocytes has anti-inflammatory effects, while signaling in fibroblast-like synoviocytes, myocytes, osteoblasts, and osteocytes has pro-inflammatory actions in rheumatoid arthritis. Conversely, in osteoarthritis, endogenous glucocorticoid signaling in both osteoblasts and chondrocytes has destructive actions. Together these studies provide insights into the role of endogenous glucocorticoids in the pathogenesis of both inflammatory and degenerative joint disease.



中文翻译:

关节炎和内源性糖皮质激素的作用。

类风湿性关节炎和骨关节炎是最常见的关节炎形式,是慢性、疼痛和致残的病症。尽管这两种疾病的病因不同,但它们都表现为进行性关节破坏,其特征是关节软骨、骨和滑膜的病理变化。虽然治疗性(即外源性)糖皮质激素的强效抗炎特性已被大量研究并广泛用于临床实践,但内源性糖皮质激素在关节炎易感性和疾病进展中的作用仍知之甚少。来自小鼠模型的当前证据表明,局部内源性糖皮质激素信号被类风湿性关节炎的促炎微环境和骨关节炎的衰老相关机制上调。此外,这些模型表明巨噬细胞、肥大细胞和软骨细胞中的内源性糖皮质激素信号具有抗炎作用,而成纤维细胞样滑膜细胞、肌细胞、成骨细胞和骨细胞中的信号在类风湿性关节炎中具有促炎作用。相反,在骨关节炎中,成骨细胞和软骨细胞中的内源性糖皮质激素信号具有破坏性作用。这些研究共同为内源性糖皮质激素在炎症和退行性关节病发病机制中的作用提供了见解。成骨细胞和软骨细胞中的内源性糖皮质激素信号具有破坏性作用。这些研究共同为内源性糖皮质激素在炎症和退行性关节病发病机制中的作用提供了见解。成骨细胞和软骨细胞中的内源性糖皮质激素信号具有破坏性作用。这些研究共同为内源性糖皮质激素在炎症和退行性关节病发病机制中的作用提供了见解。

更新日期:2020-09-08
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