Binding of carbon nanotube to BMP receptor 2 enhances cell differentiation and inhibits apoptosis via regulating bHLH transcription factors

Y Zhang,M F Roussel,H Zhou,K Vrijens,G Jiang,B Yan,Q Mu

doi:10.1038/cddis.2012.48

Abstract

Biomaterials that can drive stem cells to an appropriate differentiation level and decrease apoptosis of transplanted cells are needed in regenerative medicine. Nanomaterials are promising novel materials for such applications. Here we reported that carboxylated multiwalled carbon nanotube (MWCNT 1) promotes myogenic differentiation of mouse myoblast cells and inhibits cell apoptosis under the differentiation conditions by regulating basic helix-loop-helix transcription factors. MWCNT 1 attenuates bone morphogenetic protein receptor (BMPR) signaling activity by binding to BMPR2 and attenuating the phosphorylation of BMPR1. This molecular understanding allowed us to tune stem cell differentiation to various levels by chemical modifications, demonstrating human control of biological activities of nanoparticles and opening an avenue for potential applications of nanomaterials in regenerative medicine.

Highlights

Adult stem cells, the undifferentiated cells residing in mature organs or tissues, can renew themselves and differentiate to cells of the specialized tissues or organs
MWCNT 1 improved cell survival under the differentiation conditions. These effects were originated from the binding of MWCNT 1 to bone morphogenetic protein receptor 2 (BMPR2), suppressing the BMP signaling pathway and regulating basic helixloop-helix transcription factors involved in differentiation and apoptosis
We have reported that carbon nanotube (CNT) inhibit the BMP signaling pathway[28] and this was confirmed by MWCNT 1 perturbs the phosphorylation of BMPR1

Summary

Introduction

The undifferentiated cells residing in mature organs or tissues, can renew themselves and differentiate to cells of the specialized tissues or organs. Induction of myogenic differentiation from different adult stem cells is promising to cure diseases like muscular dystrophies,[6] cardiac myocyte death[7] and muscle damage. MWCNT 1 improved cell survival under the differentiation conditions These effects were originated from the binding of MWCNT 1 to bone morphogenetic protein receptor 2 (BMPR2), suppressing the BMP signaling pathway and regulating basic helixloop-helix (bHLH) transcription factors involved in differentiation and apoptosis. Based on this mechanistic understanding, we successfully modulated myogenic differentiation of C2C12 to various levels by surface-chemistry modifications on MWCNTs

Methods

Results

Conclusion