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

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Methylprednisolone acetate mitigates IL1β induced changes in matrix metalloproteinase gene expression in skeletally immature ovine explant knee tissues
Inflammation Research ( IF 6.7 ) Pub Date : 2020-11-23 , DOI: 10.1007/s00011-020-01421-2
Kristen I Barton _{1,

2,

3} , May Chung ₂ , Cyril B Frank _{1,

2,

3,

4} , Nigel G Shrive _{1,

4} , David A Hart _{2,

4,

5}

Affiliation

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 (10⁻³ M), (3) MPA (10⁻⁴ M), (4) IL1β, (5) IL1β + 10⁻³ M MPA, or (6) IL1β + 10⁻⁴ 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_T 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.

中文翻译：

醋酸甲泼尼龙减轻 IL1β 诱导的骨骼未成熟绵羊外植体膝关节组织中基质金属蛋白酶基因表达的变化

目标和设计

本研究旨在评估甲基强的松龙 (MPA) 对白介素 (IL)1β 诱导后未成熟绵羊膝关节组织外植体中信使核糖核酸 (mRNA) 表达水平的影响，并评估外植体的反应性。

材料或科目

从未成熟的雌性绵羊的关节软骨、滑膜和髌下脂肪垫 (IPFP) 中收获外植体。

治疗

甲基强的松龙。

方法

样品分为六组：(1) 对照，(2) MPA (10 ^-3 M)，(3) MPA (10 ^-4 M)，(4) IL1β，(5) IL1β + 10 ^-3 M MPA ，或 (6) IL1β + 10 ^-4 M MPA。量化了与炎症、软骨降解/合成代谢、先天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 _T方法比较 MPA 处理的倍数变化。

结果

甲基强的松龙治疗显着抑制软骨（MMP1、MMP3 和 MMP13）、滑膜（MMP1 和 MMP3）和 IPFP（MMP13）中的 MMP（所有p < 0.05）。其他较少受到抑制的基因包括内源性 IL1β（软骨）和 IL6（IPFP）（所有p < 0.05），其他不受 IL-1 暴露或随后 MPA 影响的基因包括 TGFβ1、TLR4 和脂肪相关分子。