Vitamin D Promotes MSC Osteogenic Differentiation Stimulating Cell Adhesion and <i>α</i>V<i>β</i>3 Expression

Abstract

Vitamin D (Vit D) by means of its biological active form, 1<i>α</i>,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), has a protective effect on the skeleton by acting on calcium homeostasis and bone formation. Furthermore, Vit D has a direct effect on mesenchymal stem cells (MSCs) in stimulating their osteogenic differentiation. In this work, we present for the first time the effect of 1,25(OH)₂D₃ on MSC adhesion. Considering that cell adhesion to the substrate is fundamental for cell commitment and differentiation, we focused on the expression of <i>α</i>_V<i>β</i>₃ integrin, which has a key role in the commitment of MSCs to the osteoblastic lineage. Our data indicate that Vit D increases <i>α</i>_V<i>β</i>₃ integrin expression inducing the formation of focal adhesions (FAs). Moreover, we assayed MSC commitment in the presence of the extracellular matrix (ECM) glycoprotein fibronectin (FN), which is able to favor cell adhesion on surfaces and also to induce osteopontin (OPN) expression: this suggests that Vit D and FN synergize in supporting cell adhesion. Taken together, our findings provide evidence that Vit D can promote osteogenic differentiation of MSCs through the modulation of <i>α</i>_V<i>β</i>₃ integrin expression and its subcellular organization, thus favoring binding with the matrix protein (FN).