α10 Integrin Expression Is Up-Regulated on Fibroblast Growth Factor-2-Treated Mesenchymal Stem Cells with Improved Chondrogenic Differentiation Potential

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells that have the capacity to differentiate into various different cell lineages and can generate bone, cartilage and adipose tissue. MSCs are presently characterized using a broad range of different cell-surface markers that are not exclusive to MSCs and not sensitive to culture conditions or differentiation capacity. We show that the integrin subunits alpha10 and alpha11 of the collagen binding integrins alpha10beta1 and alpha11beta1 are expressed by human MSCs in monolayer cultures. We also demonstrate that the expression of alpha10 increases, while alpha1 and alpha11 decrease, during aggregate culture of MSCs in chondrogenic medium. Alpha10beta1 is expressed by chondrocytes in cartilage, whereas alpha11beta1 integrins are predominantly expressed by subsets of the fibroblastic lineage. In extensive monolayer cultures of MSCs, alpha10 expression is down-regulated. We show that this down-regulation is reversed by fibroblast growth factor-2 (FGF-2) treatment. Addition of FGF-2 to MSCs not only results in increased alpha10 expression, but also in decreased alpha11 expression. FGF-2 treatment of MSCs has been shown to keep the cells more multipotent and also induces cell proliferation and Sox-9 up-regulation. We demonstrate improved chondrogenecity as well as increased collagen-dependant migratory potential of FGF-2-treated MSCs having a high alpha10 expression. We also demonstrate expression of alpha10 and alpha11 integrin subunits in the endosteum and periosteum of mice, but very low or not detectable expression levels in freshly aspired human or mouse BM. We show that MSCs with high chondrogenic differentiation potential are highly alpha10 positive and propose alpha10 as a potential marker to predict the differentiation state of MSCs.

The integrin–collagen connection – a glue for tissue repair?

“…Interestingly, the area around forming bone is rich in mesenchymal stem cells, and the treatment of these with fibroblast growth factor 2 (FGF2) concomitantly induces expression of integrin α10 and that of a chondrogenic phenotype (Varas et al, 2007). Furthermore, ITGA10 mRNA expression is induced in bonemarrow-derived mesenchymal stem cells because these cells form the chondrogenic niches that are needed to establish a bone marrow microenvironment (Reinisch et al, 2015).…”

Inhibition of Ovarian Tumor Growth by Targeting the HU177 Cryptic Collagen Epitope

“…53 Moreover, mesenchymal stem cells have also been implicated as potential sources of a-SMAe expressing CAF-like cells in tumors. 54 In addition, studies now suggest enhanced expression of a 10 b 1 in melanoma cell lines compared with primary melanocytes and inhibiting a 10 b 1 in these cells resulted in a reduced migration.…”

Contribution of collagen adhesion receptors to tissue fibrosis

“…In mesenchymal stem cells, α10β1 integrin expression that is induced by FGF-2 is associated with enhanced type II collagen synthesis. These data indicate that the α10 integrin is a potential biomarker of the pluripotency of mesenchymal stem cells and could be harnessed to induce chondrogenesis in cartilage tissue engineering (LundgrenÅkerlund and Aszòdi 2014; Varas et al 2007).…”