α10 Integrin expression is up-regulated on fibroblast growth factor-2-treated mesenchymal stem cells with improved chondrogenic differentiation potential

Laura Varas, Lars Bryngelson Ohlsson, Gabriella Honeth, Andreas Olsson, Therese Bengtsson, Charlotte Wiberg, Robert Bockermann, Sofia Järnum, Johan Richter, Douglas Pennington, Brian Johnstone, Evy Lundgren-Åkerlund, Christian Kjellman

Research output: Contribution to journalArticle

53 Citations (Scopus)

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 α10 and α11 of the collagen binding integrins α10β1 and α11β1 are expressed by human MSCs in monolayer cultures. We also demonstrate that the expression of α10 increases, while α1 and α11 decrease, during aggregate culture of MSCs in chondrogenic medium. α10β1 is expressed by chondrocytes in cartilage, whereas α11β1 integrins are predominantly expressed by subsets of the fibroblastic lineage. In extensive monolayer cultures of MSCs, α10 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 α10 expression, but also in decreased α11 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 α10 expression. We also demonstrate expression of α10 and α11 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 α10 positive and propose α10 as a potential marker to predict the differentiation state of MSCs.

Original languageEnglish (US)
Pages (from-to)965-978
Number of pages14
JournalStem Cells and Development
Volume16
Issue number6
DOIs
StatePublished - Dec 1 2007

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Fibroblast Growth Factor 2
Mesenchymal Stromal Cells
Integrins
Cartilage
Collagen
Periosteum
Cell Lineage
Chondrocytes
Adipose Tissue
Up-Regulation
Down-Regulation
Cell Proliferation
Bone and Bones

ASJC Scopus subject areas

  • Hematology

Cite this

α10 Integrin expression is up-regulated on fibroblast growth factor-2-treated mesenchymal stem cells with improved chondrogenic differentiation potential. / Varas, Laura; Ohlsson, Lars Bryngelson; Honeth, Gabriella; Olsson, Andreas; Bengtsson, Therese; Wiberg, Charlotte; Bockermann, Robert; Järnum, Sofia; Richter, Johan; Pennington, Douglas; Johnstone, Brian; Lundgren-Åkerlund, Evy; Kjellman, Christian.

In: Stem Cells and Development, Vol. 16, No. 6, 01.12.2007, p. 965-978.

Research output: Contribution to journalArticle

Varas, L, Ohlsson, LB, Honeth, G, Olsson, A, Bengtsson, T, Wiberg, C, Bockermann, R, Järnum, S, Richter, J, Pennington, D, Johnstone, B, Lundgren-Åkerlund, E & Kjellman, C 2007, 'α10 Integrin expression is up-regulated on fibroblast growth factor-2-treated mesenchymal stem cells with improved chondrogenic differentiation potential', Stem Cells and Development, vol. 16, no. 6, pp. 965-978. https://doi.org/10.1089/scd.2007.0049
Varas, Laura ; Ohlsson, Lars Bryngelson ; Honeth, Gabriella ; Olsson, Andreas ; Bengtsson, Therese ; Wiberg, Charlotte ; Bockermann, Robert ; Järnum, Sofia ; Richter, Johan ; Pennington, Douglas ; Johnstone, Brian ; Lundgren-Åkerlund, Evy ; Kjellman, Christian. / α10 Integrin expression is up-regulated on fibroblast growth factor-2-treated mesenchymal stem cells with improved chondrogenic differentiation potential. In: Stem Cells and Development. 2007 ; Vol. 16, No. 6. pp. 965-978.
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AU - Varas, Laura

AU - Ohlsson, Lars Bryngelson

AU - Honeth, Gabriella

AU - Olsson, Andreas

AU - Bengtsson, Therese

AU - Wiberg, Charlotte

AU - Bockermann, Robert

AU - Järnum, Sofia

AU - Richter, Johan

AU - Pennington, Douglas

AU - Johnstone, Brian

AU - Lundgren-Åkerlund, Evy

AU - Kjellman, Christian

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AB - 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 α10 and α11 of the collagen binding integrins α10β1 and α11β1 are expressed by human MSCs in monolayer cultures. We also demonstrate that the expression of α10 increases, while α1 and α11 decrease, during aggregate culture of MSCs in chondrogenic medium. α10β1 is expressed by chondrocytes in cartilage, whereas α11β1 integrins are predominantly expressed by subsets of the fibroblastic lineage. In extensive monolayer cultures of MSCs, α10 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 α10 expression, but also in decreased α11 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 α10 expression. We also demonstrate expression of α10 and α11 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 α10 positive and propose α10 as a potential marker to predict the differentiation state of MSCs.

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