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骨关节炎人类软骨细胞炎症的性别特异性降低与营养保健品依赖的细胞外基质形成

Sex-Specific Reduction in Inflammation of Osteoarthritic Human Chondrocytes and Nutraceutical-Dependent Extracellular Matrix Formation.

作者信息

Mallah Alia, Amr Mahmoud, Abusharkh Haneen, Wie Bernard Van, Gozen Arda, Mendenhall Juana, Tingstad Edwin, Idone Vincent, Abu-Lail Nehal I

机构信息

Department of Biomedical Engineering and Chemical Engineering, The University of Texas at San Antonio (UTSA), San Antonio, TX.

Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Washington State University (WSU), Pullman, WA.

出版信息

J Immunol Regen Med. 2021 Nov;14. doi: 10.1016/j.regen.2021.100054. Epub 2021 Oct 8.

DOI:10.1016/j.regen.2021.100054
PMID:34796310
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8594870/
Abstract

INTRODUCTION

The aim of this study was to investigate the ability of osteoarthritic human chondrocytes to produce articular cartilage (AC) tissues with a reduced inflammatory environment in response to 4 anti-inflammatory nutraceuticals: alpha-tocopherol (Alpha), gallic acid (G), ascorbic acid (AA), and catechin hydrate (C).

METHODS

Chondrocytes isolated from patients who underwent total knee arthroplasty surgeries were divided into groups (9 male; mean age, 66.2 ± 3.5 years and 11 female; mean age, 64.2 ± 3.1 years). Cells were cultured based on sex and supplemented with either a negative control (NC) medium or NC plus one of the nutraceuticals at a concentration of 50 μM. At day 21, cultures were characterized histologically, biochemically, and for gene expression of vital markers.

RESULTS

At day 21, 62.3% and 66.2% reduction in nitric oxide (NO) content was evident for female and male cells, respectively. G-treatment of female cells resulted in the lowest expression of nitric oxide synthase-2 (NOS2), matrix metalloproteinase-13 (MMP13), and collagen type-10 (COL10). Alpha-treatment of male cells resulted in the lowest expression of NOS2, bone morphogenic protein-2, MMP13, COL10 and tumor necrosis factor alpha induced protein-6 (TNFAIP6) relative to NC. AA and Alpha treatment resulted in the highest glycosaminoglycan (GAG) content for female and male cultures, respectively.

CONCLUSION

A sex-dependent response of osteoarthritic chondrocytes to nutraceutical treatment was evident. Our results suggest the use of G for female cells and Alpha for male cells in OA applications seems to be favorable in reducing inflammation and enhancing chondrocytes' ability to form AC tissues.

摘要

引言

本研究旨在探讨骨关节炎患者的软骨细胞在4种抗炎营养保健品作用下,生成炎症环境减轻的关节软骨(AC)组织的能力。这4种抗炎营养保健品分别为:α-生育酚(Alpha)、没食子酸(G)、抗坏血酸(AA)和儿茶素水合物(C)。

方法

从接受全膝关节置换手术的患者中分离出软骨细胞,分为不同组(9名男性,平均年龄66.2±3.5岁;11名女性,平均年龄64.2±3.1岁)。根据性别对细胞进行培养,并添加阴性对照(NC)培养基或浓度为50μM的NC加一种营养保健品。在第21天,对培养物进行组织学、生物化学特征分析以及关键标志物的基因表达分析。

结果

在第21天,女性和男性细胞中的一氧化氮(NO)含量分别显著降低了62.3%和66.2%。用G处理女性细胞导致一氧化氮合酶-2(NOS2)、基质金属蛋白酶-13(MMP13)和10型胶原蛋白(COL10)的表达最低。相对于NC,用Alpha处理男性细胞导致NOS2、骨形态发生蛋白-2、MMP13、COL10和肿瘤坏死因子α诱导蛋白-6(TNFAIP6)的表达最低。AA和Alpha处理分别使女性和男性培养物中的糖胺聚糖(GAG)含量最高。

结论

骨关节炎软骨细胞对营养保健品治疗存在性别依赖性反应。我们的结果表明,在骨关节炎应用中,对女性细胞使用G,对男性细胞使用Alpha,似乎有利于减轻炎症并增强软骨细胞形成AC组织的能力。

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