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整合素 α2β1 在人关节软骨来源的软骨细胞与去端肽胶原凝胶的相互作用中发挥重要作用。

Integrin α2β1 plays an important role in the interaction between human articular cartilage-derived chondrocytes and atelocollagen gel.

机构信息

Department of Medicine for Sports and Performing Arts, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Department of Musculoskeletal Regenerative Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

出版信息

Sci Rep. 2021 Jan 19;11(1):1757. doi: 10.1038/s41598-021-81378-2.

DOI:10.1038/s41598-021-81378-2
PMID:33469078
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7815876/
Abstract

Although atelocollagen gel is used as a scaffold for culturing human articular cartilage-derived chondrocytes, little is known about cell-gel interactions. In this study, we investigated the mechanism via which atelocollagen gel affects human articular cartilage-derived chondrocytes. Two types of three-dimensional cultures of human articular cartilage-derived chondrocytes (i.e., with and without atelocollagen gel) were compared. While the amount of atelocollagen gel in culture gradually decreased with time, it promoted the expression of matrix metalloproteinases (MMPs) during the early stages of culture. Genome-wide differential gene expression analysis revealed that cell membrane- and extracellular matrix-related genes were highly ranked among up- and down-regulated groups in cells cultured in the presence of atelocollagen gel. Among the integrin family of genes, the expression of integrin subunit alpha 2 and integrin subunit alpha 10 was significantly increased in the presence of atelocollagen gel. Blocking α2β1 integrin with the specific inhibitor BTT 3033 had a significant effect on cell proliferation, MMP expression, and cell shape, as well as on the response to mechanical stimulation. Taken together, our findings indicate that the α2β1 integrin pathway plays an important role in the interaction of atelocollagen gel with human articular cartilage-derived chondrocytes and may be a potential therapeutic target for articular cartilage disorders.

摘要

虽然明胶凝胶被用作培养人关节软骨来源的软骨细胞的支架，但对于细胞-凝胶相互作用知之甚少。在这项研究中，我们研究了明胶凝胶影响人关节软骨来源的软骨细胞的机制。比较了两种类型的人关节软骨来源的软骨细胞的三维培养（即有和没有明胶凝胶）。虽然明胶凝胶在培养中的含量随着时间的推移逐渐减少，但它在培养的早期阶段促进了基质金属蛋白酶（MMPs）的表达。全基因组差异基因表达分析显示，在有明胶凝胶存在的情况下培养的细胞中，细胞膜和细胞外基质相关基因在上调和下调组中排名很高。在整合素家族基因中，整合素亚基α2 和整合素亚基α10 的表达在明胶凝胶存在的情况下显著增加。用特异性抑制剂 BTT 3033 阻断 α2β1 整合素对细胞增殖、MMP 表达和细胞形态以及对机械刺激的反应有显著影响。综上所述，我们的研究结果表明，α2β1 整合素途径在明胶凝胶与人关节软骨来源的软骨细胞相互作用中起着重要作用，可能是关节软骨疾病的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71a9/7815876/9dfb7745e623/41598_2021_81378_Fig7_HTML.jpg
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