Vitronectin and collagen I differentially regulate osteogenesis in mesenchymal stem cells

• Published in: Biochemical and biophysical research communications 2006-08, Vol.347 (1), p.347-357
• Main Authors: Kundu, Anup K., Putnam, Andrew J.
• Format: Article
• Language: English
• Subjects: Adsorption; Cell Adhesion - physiology; Cell Culture Techniques - methods; Cell Differentiation - physiology; Cells, Cultured; Collagen Type I - metabolism; Differentiation; Extracellular matrix; Extracellular Matrix - physiology; Focal adhesions; Humans; Integrins; Integrins - metabolism; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Osteoblasts - cytology; Osteoblasts - metabolism; Osteogenesis; Osteogenesis - physiology; Signal transduction; Tissue Engineering - methods; Vitronectin - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.06.110

The roles of various soluble factors in promoting the osteogenic differentiation of adult mesenchymal stem cells (MSCs) have been widely studied, but little is known about how the extracellular matrix (ECM) instructs the phenotypic transition between growth and differentiation. To investigate this question, we cultured MSCs on purified vitronectin or type-I collagen, motivated by our earlier tissue engineering work demonstrating that MSC adhesion to polymer scaffolds is primarily mediated by the passive adsorption of these two ECM ligands from serum. Using alkaline phosphatase activity and matrix mineralization as indicators of the early and late stages of osteogenesis, respectively, we report here that both substrates supported differentiation, but the mechanism was substrate dependent. Specifically, osteogenesis on vitronectin correlated with enhanced focal adhesion formation, the activation of focal adhesion kinase (FAK) and paxillin, and the diminished activation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3 kinase (PI3K) pathways. By contrast, MSCs on type-I collagen exhibited reduced focal adhesion formation, reduced activation of FAK and paxillin, and increased activation of ERK and PI3K. Inhibition of ERK and FAK blocked mineral deposition on both substrates, suggesting that the observed differences in signaling pathways ultimately converge to the same cell fate. Understanding these mechanistic differences is essential to predictably control the osteogenic differentiation of MSCs and widen their use in regenerative medicine.