title: Differentiation of human skeletal muscle stem cells into odontoblasts is dependent on induction of α1 integrin expression.
abstract: 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(+)hSMSCs) 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(+)hSMSCs were treated in suspension with retinoic acid followed by culture on a gelatin scaffold in the presence of BMP-4. Following this protocol, α7(+)hSMSCs were induced to down-regulate myogenic genes (MYOD and α7 integrin) and up-regulate odontogenic markers including dentin sialophosphoprotein, matrix metalloproteinase-20 (enamelysin), dentin sialoprotein, and alkaline phosphatase but not osteoblastic genes (osteopontin and osteocalcin). Following retinoic acid and gelatin scaffold/BMP-4 treatment, there was a coordinated switch in the integrin expression profile that paralleled odontoblastic differentiation where α1β1 integrin was strongly up-regulated 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 dentin sialophosphoprotein and matrix metalloproteinase-20. These results strongly suggest that the differentiation of α7(+)hSMSCs along the odontogenic lineage is dependent on the concurrent expression of α1 integrin.
authors.affiliation: From the Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Ozeki
authors.affiliation: Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, Nagoya 464-8650, Japan, and.
authors.forename: Makio
authors.initials: M
authors.lastname: Mogi
authors.affiliation: From the Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamaguchi
authors.affiliation: From the Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Hiyama
authors.affiliation: From the Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Kawai
authors.affiliation: From the Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Hase
authors.affiliation: From the Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakata
authors.affiliation: From the Department of Endodontics, School of Dentistry, Aichi Gakuin University, Nagoya, Aichi 464-8651, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Cell and Tissue Biology, University of California, San Francisco, California 94143 randall.kramer@ucsf.edu.
authors.forename: Randall H
authors.initials: RH
authors.lastname: Kramer
mesh_terms: D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D053595:Embryonic Stem Cells / Q000166:cytology*; D020868:Gene Silencing; D006801:Humans; D039423:Integrin alpha1 / Q000235:genetics*; D018482:Muscle, Skeletal / Q000166:cytology*; D009804:Odontoblasts / Q000166:cytology*; D009805:Odontogenesis; D034741:RNA, Small Interfering / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: D039423:Integrin alpha1; D034741:RNA, Small Interfering
keywords: BMP-4; Bone Morphogenetic Protein (BMP); Cell Adhesion; Cell Motility; Integrins; Muscle; Odontoblast; Retinoic Acid; Stem Cells