Alpha10 integrin expression is up-regulated on fibroblast growth factor-2-treated mesenchymal stem cells with improved chondrogenic differentiation potential.
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.
Cartela AB, 220 07 Lund, Sweden. laura@cartela.se
Laura
L
Varas
Lars Bryngelson
LB
Ohlsson
Gabriella
G
Honeth
Andreas
A
Olsson
Therese
T
Bengtsson
Charlotte
C
Wiberg
Robert
R
Bockermann
Sofia
S
Järnum
Johan
J
Richter
Douglas
D
Pennington
Brian
B
Johnstone
Evy
E
Lundgren-Akerlund
Christian
C
Kjellman
D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement; D019902:Chondrocytes / Q000166:cytology*; D003094:Collagen / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction; D015854:Up-Regulation
D006133:Growth Substances; D039001:Integrin alpha Chains; C406210:integrin alpha 10; D016222:Fibroblast Growth Factor 2; D003094:Collagen