Mesenchymal progenitor cells communicate via alpha and beta integrins with a three-dimensional collagen type I matrix.
OBJECTIVE
The aim of our study was to investigate interactions of mesenchymal progenitor cells (MPCs) with collagen matrices.


METHODS
Human bone-marrow-derived MPCs were cultivated in collagen type I gels with and without inhibition of beta(1)-integrin by a specific antibody. Collagen gel contraction, cell morphology, expression of integrin subunits and several genes related to matrix synthesis and turnover as well as MPC differentiation were analyzed over 14 days.


RESULTS
Human MPCs markedly contracted free-floating collagen gels. Contraction was nearly completely inhibited by blocking beta(1)-integrin. Cellular morphology was elongated in the absence and mostly round in the presence of the antibody. Expression of integrin alpha(1), alpha(2) and beta(1) subunits showed several changes partly dependent on beta(1)-integrin blocking. Expression of matrix metalloproteinase-1 was elevated irrespective of beta(1)-integrin blocking and tenascin-C was subsequently induced during gel contraction. Spontaneous induction of chondrogenic, osteogenic or adipogenic differentiation was observed neither in the presence nor in the absence of the beta(1)-integrin antibody.


CONCLUSIONS
Our results indicate that the interaction of human MPCs with fibrillar collagen type I involves beta(1)- and alpha-integrin subunits and induces changes in gene expression related to extracellular matrix synthesis and turnover but not differentiation to the chondrogenic, osteogenic or adipogenic phenotype.
Heckmann
Leslie
L
Department of Orthopedics, Division for Biochemistry of Joint and Connective Tissue Diseases, University of Ulm, Ulm, Germany.
Fiedler
Jörg
J
Mattes
Thomas
T
Brenner
Rolf E
RE
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D039423:Integrin alpha1 / Q000235:genetics / Q000378:metabolism; D039421:Integrin alpha2 / Q000235:genetics / Q000378:metabolism; D039422:Integrin alpha3 / Q000235:genetics / Q000378:metabolism; D039641:Integrin beta Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019012:Integrin beta1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019063:Tenascin / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D024042:Collagen Type I; D039001:Integrin alpha Chains; D039423:Integrin alpha1; D039421:Integrin alpha2; D039422:Integrin alpha3; D039641:Integrin beta Chains; D019012:Integrin beta1; D019063:Tenascin; D020781:Matrix Metalloproteinase 1