Differentiation of Human Skeletal Muscle Stem Cells into Odontoblasts is Dependent on Induction of {alpha}1 Integrin Expression [Developmental Biology]
April 1st, 2014 by Ozeki, N., Mogi, M., Yamaguchi, H., Hiyama, T., Kawai, R., Hase, N., Nakata, K., Nakamura, H., Kramer, R. H.
Skeletal muscle stem cells represent an abundant source of autologous cells with potential for regenerative medicine that can be directed to differentiate into multiple lineages including osteoblasts and adipocytes. In the current study, we found that α7+ integrin-positive human skeletal muscle stem cells (α7+hSMSC) could differentiate into the odontoblast lineage under specific inductive conditions in response to bone morphogenetic protein-4 (BMP-4). Cell aggregates of FACS harvested α7+hSMSC were treated in suspension with retinoic acid (RA) followed by culture on a gelatin scaffold (GS) in the presence of BMP-4. Following this protocol, α7+hSMSC were induced to down regulate myogenic genes (MyoD and α7 integrin) and upregulate odontogenic markers including dentin sialophosphoprotein (DSPP), matrix metalloproteinase-20 (MMP-20) (Enamelysin), dentin sialoprotein (DSP) and alkaline phosphatase (ALP), but not osteoblastic genes (osteopontin and osteocalcin). Following RA and GS/BMP-4 treatment there was a coordinated switch in the integrin expression profile that paralleled odontoblastic differentiation where α1β1 integrin was strongly upregulated with the attenuation of muscle-specific α7β1 integrin expression. Interestingly, using siRNA knockdown strategies revealed that the differentiation-related expression of the α1 integrin receptor positively regulates the expression of the odontoblastic markers DSPP and MMP-20. These results strongly suggest that the differentiation of α7+hSMSC along the odontogenic lineage is dependent on the concurrent expression of α1 integrin.