Posa Francesca, Di Benedetto Adriana, Cavalcanti-Adam Elisabetta A, Colaianni Graziana, Porro Chiara, Trotta Teresa, Brunetti Giacomina, Lo Muzio Lorenzo, Grano Maria, Mori Giorgio
Department of Clinical and Experimental Medicine, Medical School, University of Foggia, Foggia, Italy.
Institute of Physical Chemistry, Department of Biophysical Chemistry, University of Heidelberg and Max Planck Institute for Intelligent Systems, Stuttgart, Germany.
Stem Cells Int. 2018 Feb 28;2018:6958713. doi: 10.1155/2018/6958713. eCollection 2018.
Vitamin D (Vit D) by means of its biological active form, 1,25-dihydroxyvitamin D (1,25(OH)D), 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)D on MSC adhesion. Considering that cell adhesion to the substrate is fundamental for cell commitment and differentiation, we focused on the expression of integrin, which has a key role in the commitment of MSCs to the osteoblastic lineage. Our data indicate that Vit D increases 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 integrin expression and its subcellular organization, thus favoring binding with the matrix protein (FN).
维生素D（Vit D）通过其生物活性形式1,25 - 二羟基维生素D（1,25(OH)D），作用于钙稳态和骨形成，从而对骨骼起到保护作用。此外，Vit D对间充质干细胞（MSCs）具有直接作用，可刺激其成骨分化。在本研究中，我们首次展示了1,25(OH)D对MSCs黏附的影响。鉴于细胞与底物的黏附是细胞定向分化的基础，我们聚焦于整合素的表达，整合素在MSCs向成骨细胞谱系的定向分化中起关键作用。我们的数据表明，Vit D可增加整合素表达，诱导黏着斑（FAs）形成。此外，我们检测了在细胞外基质（ECM）糖蛋白纤连蛋白（FN）存在的情况下MSCs的定向分化，FN能够促进细胞在表面的黏附，并诱导骨桥蛋白（OPN）表达：这表明Vit D和FN在支持细胞黏附方面具有协同作用。综上所述，我们的研究结果证明，Vit D可通过调节整合素表达及其亚细胞组织，促进MSCs的成骨分化，从而有利于与基质蛋白（FN）结合。
