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醋酸甲泼尼龙可减轻未成年羊膝关节组织 explant 中白细胞介素 1β 诱导的基质金属蛋白酶基因表达变化。

Methylprednisolone acetate mitigates IL1β induced changes in matrix metalloproteinase gene expression in skeletally immature ovine explant knee tissues.

机构信息

Orthopaedic Surgery, Schulich School of Dentistry and Medicine, London Health Sciences Centre, Western University, 1151 Richmond St, London, ON, N6A 5C1, Canada.

McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

出版信息

Inflamm Res. 2021 Jan;70(1):99-107. doi: 10.1007/s00011-020-01421-2. Epub 2020 Nov 23.

DOI:10.1007/s00011-020-01421-2
PMID:33226449
Abstract

OBJECTIVE AND DESIGN

This study aimed at evaluating the effect of methylprednisolone (MPA) on messenger ribonucleic acid (mRNA) expression levels in immature ovine knee joint tissue explants following interleukin (IL)1β induction and to assess responsiveness of the explants.

MATERIAL OR SUBJECTS

Explants were harvested from the articular cartilage, synovium, and infrapatellar fat pad (IPFP) from immature female sheep.

TREATMENT

Methylprednisolone.

METHODS

The samples were allocated into six groups: (1) control, (2) MPA (10 M), (3) MPA (10 M), (4) IL1β, (5) IL1β + 10 M MPA, or (6) IL1β + 10 M MPA. mRNA expression levels for molecules relevant to inflammation, cartilage degradation/anabolism, activation of innate immunity, and adipose tissue/hormones were quantified. Fold changes with MPA treatment were compared via the comparative C method.

RESULTS

Methylprednisolone treatment significantly suppressed MMPs consistently across the cartilage (MMP1, MMP3, and MMP13), synovium (MMP1 and MMP3), and IPFP (MMP13) (all p < 0.05). Other genes that were less consistently suppressed include endogenous IL1β (cartilage) and IL6 (IPFP) (all p < 0.05), and others not affected either by IL-1 exposure or subsequent MPA include TGFβ1, TLR4, and adipose-related molecules.

CONCLUSIONS

Methylprednisolone significantly mitigated IL1β induced mRNA expression for MMPs in the immature cartilage, synovium, and IPFP, but the extent of the responsiveness was tissue-, location-, and gene-specific.

摘要

目的和设计

本研究旨在评估甲基强的松龙(MPA)对白细胞介素(IL)1β诱导的未成熟羊膝关节组织外植体信使核糖核酸(mRNA)表达水平的影响,并评估外植体的反应性。

材料或受试者

从未成熟雌性绵羊的关节软骨、滑膜和髌下脂肪垫(IPFP)中采集外植体。

治疗

甲基强的松龙。

方法

将样本分为六组:(1)对照组,(2)MPA(10μM),(3)MPA(10μM),(4)IL1β,(5)IL1β+10μM MPA,或(6)IL1β+10μM MPA。定量分析与炎症、软骨降解/合成、固有免疫激活和脂肪组织/激素相关的分子的 mRNA 表达水平。通过比较 C 法比较 MPA 处理的倍数变化。

结果

MPA 治疗显著抑制了软骨(MMP1、MMP3 和 MMP13)、滑膜(MMP1 和 MMP3)和 IPFP(MMP13)中 MMPs 的表达(均 p<0.05)。其他受抑制程度较低的基因包括内源性 IL1β(软骨)和 IL6(IPFP)(均 p<0.05),而其他不受 IL-1 暴露或随后 MPA 影响的基因包括 TGFβ1、TLR4 和与脂肪相关的分子。

结论

MPA 显著减轻了未成熟软骨、滑膜和 IPFP 中 IL1β 诱导的 MMPs mRNA 表达,但反应的程度是组织、位置和基因特异性的。

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Location and gene-specific effects of methylprednisolone acetate on mitigating IL1β-induced inflammation in mature ovine explant knee tissue.醋酸甲基泼尼松龙对减轻成熟绵羊外植体膝关节组织中白细胞介素-1β诱导的炎症的定位及基因特异性作用。
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