SRGN promotes macrophage recruitment through CCL3 in osteoarthritis.

IF 2.8 4区医学 Q3 CELL BIOLOGY

Connective Tissue Research Pub Date : 2024-07-01 Epub Date: 2024-07-27 DOI:10.1080/03008207.2024.2380313

Yi Zhang, Zihua Li, Cheng Chen, Wang Wei, Zhendong Li, Haichao Zhou, Wenbao He, Jiang Xia, Bing Li, Yunfeng Yang

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引用次数: 0

Abstract

Background: Osteoarthritis (OA) is a degenerative disease that affects synovial joints and leads to significant pain and disability, particularly in older adults. Infiltration of macrophages plays a key role in the progression of OA. However, the mechanisms underlying macrophage recruitment in OA are not fully understood.

Methods: The Serglycin (SRGN) expression pattern was analyzed, along with its association with macrophage infiltration in OA, using bioinformatic methods. SRGN expression in chondrocytes was altered by small interfering RNA (siRNA) and plasmids. Conditioned media (CM) was obtained from transfected chondrocytes to establish a co-culture model of chondrocytes and THP-1 derived macrophages. The impact of SRGN on macrophage recruitment was evaluated using a transwell assay. Furthermore, the regulatory effect of SRGN on CCL3 was validated through qPCR, WB, and ELISA experiments.

Results: In OA patients, the upregulation of SRGN positively correlated with K-L grade and macrophage infiltration. It was found that SRGN expression and secretion were up-regulated in OA and that it can promote macrophage migration in vitro. Further investigation showed that SRGN affects macrophage migration by regulating the expression of CCL3.

Conclusion: SRGN in chondrocytes plays a role in promoting the recruitment of THP-1 derived macrophages in vitro by regulating production of CCL3.

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SRGN通过CCL3促进骨关节炎中巨噬细胞的募集。

背景：骨关节炎（OA）是一种影响滑膜关节的退行性疾病，会导致严重的疼痛和残疾，尤其是在老年人中。巨噬细胞的浸润在 OA 的进展中起着关键作用。然而，人们对 OA 中巨噬细胞招募的机制还不完全清楚：方法：利用生物信息学方法分析了丝胶蛋白（SRGN）的表达模式及其与 OA 中巨噬细胞浸润的关系。通过小干扰 RNA（siRNA）和质粒改变 SRGN 在软骨细胞中的表达。从转染的软骨细胞中获得条件培养基（CM），建立软骨细胞和THP-1衍生巨噬细胞的共培养模型。利用透孔试验评估了 SRGN 对巨噬细胞募集的影响。此外，还通过qPCR、WB和ELISA实验验证了SRGN对CCL3的调节作用：结果：在 OA 患者中，SRGN 的上调与 K-L 分级和巨噬细胞浸润呈正相关。研究发现，SRGN 在 OA 中的表达和分泌均呈上调趋势，并能在体外促进巨噬细胞迁移。进一步研究发现，SRGN通过调节CCL3的表达影响巨噬细胞的迁移：结论：软骨细胞中的SRGN通过调节CCL3的产生，在体外促进THP-1衍生巨噬细胞的募集中发挥作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Connective Tissue Research 生物-细胞生物学

CiteScore

6.60

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology. The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented. The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including Biochemistry Cell and Molecular Biology Immunology Structural Biology Biophysics Biomechanics Regenerative Medicine The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.