Integrin \u03b12\u03b21 plays an important role in the interaction between human articular cartilage-derived chondrocytes and atelocollagen gel

Takashi Kanamoto,Shohei Oyama,Yoshihito Tachi,Ken Nakata,Kosuke Ebina,Takeo Mazuka,Tsuyoshi Nakai,Minami Hikida,Sanae Kuroda,Seira Sato

doi:10.1038/s41598-021-81378-2

Takashi Kanamoto, Shohei Oyama + Show 8 more

Open Access

https://doi.org/10.1038/s41598-021-81378-2

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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.

Highlights

Atelocollagen gel is used as a scaffold for culturing human articular cartilage-derived chondrocytes, little is known about cell–gel interactions
We examined the effect of cyclic compressive loading (CCL) on the production of prostaglandin E2 (PGE2), a well-known pathogenic molecule related to OA development (Fig. 7B)[21]
Several lines of evidence suggest that the interactions between atelocollagen gel and human articular cartilage-derived chondrocytes play an important role in various cellular functions

Summary

Introduction

Atelocollagen gel is used as a scaffold for culturing human articular cartilage-derived chondrocytes, little is known about cell–gel interactions. 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. 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. The use of autologous chondrocyte implantation (ACI) in humans was first reported in 1987 and is an established treatment for articular cartilage disorders of the knee. ACI involves culturing cartilage-producing cells from the knee articular cartilage and implanting them into the chondral d efect[5,6]. The authors concluded that transplanting chondrocytes in a newly formed matrix of atelocollagen gel can restore the articular cartilage of the knee[15]

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