Boron induces osteogenesis by stimulating NaBC1 in cooperation with BMPR1A

Abstract

The intrinsic properties of Mesenchymal Stem Cells (MSCs) make them ideal candidates for tissue engineering applications as they are regulated by the different signals present in the stem cell niche. Considerable efforts have been made to control stem cell behavior by designing material system approaches to engineer synthetic extracellular matrices and/or include soluble factors in the media. This work proposes a novel and simple approach based on ion-channel stimulation to determine stem cell fate that avoids the use of growth factors (GFs). We used boron ion - essential item in cell metabolism - transported inside cells by the NaBC1-channel. Addition of boron alone enhanced MSC adhesion and contractility, promoted osteogenesis and inhibited adipogenesis. The stimulated NaBC1 promoted osteogenesis via activation of the BMP canonical pathway (comprising Smad1 and YAP nucleus translocation and osteopontin expression) through a mechanism that involves simultaneous NaBC1/BMPR1A and NaBC1/5{beta}1/v{beta}3 co-localization. We describe a novel function for NaBC1 as a mechanosensitive ion-channel capable of interacting and stimulating GF receptors and fibronectin-binding integrins. Our results open up new biomaterial engineering approaches for biomedical applications by a cost-effective strategy that avoids the use of soluble GFs.