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糖皮质激素在体外对关节细胞产生具有上下文依赖性的影响。

Glucocorticoids exert context-dependent effects on cells of the joint in vitro.

机构信息

Cartilage Biology and Biomarkers, Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730 Herlev, Denmark.

出版信息

Steroids. 2011 Dec 11;76(13):1474-82. doi: 10.1016/j.steroids.2011.07.018. Epub 2011 Aug 10.

Abstract

INTRODUCTION

Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthritis. This study aimed at characterizing the effect of glucocorticoids on chondrocytes, osteoclasts, and osteoblasts.

EXPERIMENTAL

We used four model systems to investigate how glucocorticoids affect the cells of the joint; two intact tissues (femoral head- and cartilage-explants), and two separate cell cultures of osteoblasts (2T3-pre-osteoblasts) and osteoclasts (CD14(+)-monocytes). The model systems were cultured in the presence of two glucocorticoids; prednisolone or dexamethasone. To induce anabolic and catabolic conditions, cultures were activated by insulin-like growth factor I/bone morphogenetic protein 2 and oncostatin M/tumor necrosis factor-α, respectively. Histology and markers of bone- and cartilage-turnover were used to evaluate effects of glucocorticoid treatment.

RESULTS

Prednisolone treatment decreased collagen type-II degradation in immature cartilage, whereas glucocorticoids did not affect collagen type-II in mature cartilage. Glucocorticoids had an anti-catabolic effect on catabolic-activated cartilage from a bovine stifle joint and murine femoral heads. Glucocorticoids decreased viability of all bone cells, leading to a reduction in osteoclastogenesis and bone resorption; however, bone morphogenetic protein 2-stimulated osteoblasts increased bone formation, as opposed to non-stimulated osteoblasts.

CONCLUSIONS

Using highly robust in vitro models of bone and cartilage turnover, we suggest that effects of glucocorticoids highly depend on the activation and differential stage of the cell targeted in the joint. Present data indicated that glucocorticoid treatment may be beneficial for articular cartilage, although detrimental effects on bone should be taken into account.

摘要

简介

糖皮质激素在体内已知会减弱成骨作用,导致骨量减少和骨折风险增加,而对关节组织的影响则不太明显。然而,糖皮质激素似乎对骨关节炎的炎症和疼痛有减轻作用。本研究旨在研究糖皮质激素对软骨细胞、破骨细胞和成骨细胞的影响。

实验

我们使用了四个模型系统来研究糖皮质激素如何影响关节细胞;两个完整的组织(股骨头和软骨外植体)和两个单独的成骨细胞(2T3-前成骨细胞)和破骨细胞(CD14(+)单核细胞)的细胞培养物。模型系统在两种糖皮质激素;泼尼松龙或地塞米松的存在下进行培养。为了诱导合成代谢和分解代谢条件,培养物分别通过胰岛素样生长因子 I/骨形态发生蛋白 2 和肿瘤坏死因子-α/骨保护素 M 激活。组织学和骨软骨转换标志物用于评估糖皮质激素治疗的效果。

结果

泼尼松龙治疗可减少未成熟软骨中胶原 II 型的降解,而糖皮质激素对成熟软骨中的胶原 II 型无影响。糖皮质激素对牛膝关节和鼠股骨头的分解代谢激活软骨具有抗分解代谢作用。糖皮质激素降低了所有成骨细胞的活力,导致破骨细胞生成和骨吸收减少;然而,骨形态发生蛋白 2 刺激的成骨细胞增加了骨形成,而非刺激的成骨细胞则减少了骨形成。

结论

使用高度稳健的骨和软骨转换体外模型,我们认为糖皮质激素的作用高度取决于在关节中靶向的细胞的激活和差异阶段。目前的数据表明,糖皮质激素治疗可能对关节软骨有益,尽管应考虑其对骨骼的不利影响。

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