蛋白酶激活受体 2 和组织蛋白酶在骨关节炎猫和非骨关节炎猫关节中的表达。
Protease activated receptor 2 and matriptase expression in the joints of cats with and without osteoarthritis.
机构信息
Department of Veterinary Preclinical Sciences, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor Darul Ehsan, Malaysia.
School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
出版信息
J Feline Med Surg. 2021 Aug;23(8):794-803. doi: 10.1177/1098612X20977796. Epub 2020 Dec 7.
OBJECTIVES
The aim of this study was to determine the presence of protease-activated receptor 2 (PAR2) and matriptase proteins and quantify PAR2 and matriptase mRNA expression in the articular cartilage and synovial membrane of cats with and without osteoarthritis (OA).
METHODS
A total of 28 articular cartilage samples from adult cats (14 OA and 14 normal), 10 synovial membranes from adult cats (five OA and five normal) and three cartilage samples from 9-week-old fetal cats were used. The presence of PAR2 and matriptase in the cartilage and synovial membrane of the adult samples was detected by immunohistochemical (IHC) staining, while real-time PCR was used for mRNA expression analyses in all samples.
RESULTS
PAR2 was detected in all OA and normal articular cartilage and synovial membrane samples but confined to only a few superficial chondrocytes in the normal samples. Matriptase was only detected in OA articular cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression were, however, detected in all cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression levels in OA articular cartilage were five ( <0.001) and 3.3 ( <0.001) times higher than that of the healthy group, respectively. There was no significant difference ( = 0.05) in the OA synovial membrane PAR2 and matriptase mRNA expression compared with the normal samples.
CONCLUSIONS AND RELEVANCE
Detection of PAR2 and matriptase proteins and gene expression in feline articular tissues is a novel and important finding, and supports the hypothesis that serine proteases are involved in the pathogenesis of feline OA. The consistent presence of PAR2 and matriptase protein in the cytoplasm of OA chondrocytes suggests a possible involvement of proteases in cartilage degradation. Further investigations into the PAR2 and matriptase pathobiology could enhance our understanding of the proteolytic cascades in feline OA, which might lead to the development of novel therapeutic strategies.
目的
本研究旨在确定蛋白酶激活受体 2（PAR2）和组织蛋白酶原 2（matriptase）蛋白在患有和不患有骨关节炎（OA）的猫的关节软骨和滑膜中的存在，并定量分析 PAR2 和 matriptase mRNA 的表达。
方法
共使用了 28 个来自成年猫的关节软骨样本（14 个 OA 样本和 14 个正常样本）、10 个来自成年猫的滑膜样本（5 个 OA 样本和 5 个正常样本）和 3 个来自 9 周龄胎猫的软骨样本。通过免疫组织化学（IHC）染色检测成年样本中软骨和滑膜中 PAR2 和 matriptase 的存在，同时对所有样本进行实时 PCR 分析以检测 mRNA 表达。
结果
PAR2 在所有 OA 和正常关节软骨和滑膜样本中均有检测到，但仅在正常样本中的少数浅层软骨细胞中存在。matriptase 仅在 OA 关节软骨和滑膜样本中检测到。然而，PAR2 和 matriptase mRNA 在所有软骨和滑膜样本中均有表达。OA 关节软骨中的 PAR2 和 matriptase mRNA 表达水平分别比健康组高 5 倍（ <0.001）和 3.3 倍（ <0.001）。OA 滑膜中的 PAR2 和 matriptase mRNA 表达与正常样本相比无显著差异（ = 0.05）。
结论和相关性
在猫关节组织中检测到 PAR2 和 matriptase 蛋白和基因表达是一个新颖且重要的发现，支持丝氨酸蛋白酶参与猫 OA 发病机制的假说。PAR2 和 matriptase 蛋白在 OA 软骨细胞细胞质中的一致存在表明蛋白酶可能参与软骨降解。进一步研究 PAR2 和 matriptase 的病理生物学可能会增强我们对猫 OA 中蛋白水解级联的理解，这可能会导致新的治疗策略的发展。
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