Osteoinductive effects of 1α, 25 Dihydroxyvitamin D3 on human mesenchymal stem cells.

Abstract

Bone healing poses a challenge for clinicians due to the bone’s poor regenerative property. While autologous bone grafting remains the most common solution for bone defects, it causes various proven side effects. Recent developments seem to suggest that cell-based bone tissue engineering (BTE) involving human mesenchymal stem cells (hMSCs) is a more viable solution. This project aims to characterize the proliferative and osteoinductive effects of 1,25-(OH)2-D3 on hMSCs, by subjecting the cells to various concentrations of 1,25-(OH)2-D3 in vitro. Our results highlighted the dose-dependent growth inhibitory effects on hMSCs after 1,25-(OH)2-D3 administration. In addition, we have shown that supra-physiological concentrations (1 nM and 10 nM) of 1,25-(OH)2-D3 up-regulated various osteogenic markers including alkaline phosphatase (ALP) activity, extracellular mineralization, osteocalcin secretion, mRNA expression of osteocalcin and osteopontin , and also promoted early onset of hMSC morphological changes. Conversely, physiological concentrations (0.05 nM and 0.1 nM) of 1,25-(OH)2-D3 produced limited osteoinductive effects in vitro. As a practical application, 1,25-(OH)2-D3 was encapsulated in a nanoparticle, PEGylated polyaspartic acid with L-phenylalanine side chains (PAph-5), as a vehicle for in vitro delivery to hMSCs. This project has underlined the clinical implications of 1,25-(OH)2-D3 and demonstrated its potential application to BTE with the aid of nanotechnology.

*I will like to express my gratitude to Institute of Bioengineering and Nanotechnology (IBN), IBN Youth Research Program, Biomedical Research Council and A*STAR, for their support that made this work possible.