Novel SCRG1/BST1 axis regulates self-renewal, migration, and osteogenic differentiation potential in mesenchymal stem cells

Emiko Aomatsu; Noriko Takahashi; Shunsuke Sawada; Naoto Okubo; Tomokazu Hasegawa; Masayuki Taira; Hiroyuki Miura; Akira Ishisaki; Naoyuki Chosa

doi:10.1038/srep03652

Novel SCRG1/BST1 axis regulates self-renewal, migration, and osteogenic differentiation potential in mesenchymal stem cells

Sci Rep. 2014 Jan 13:4:3652. doi: 10.1038/srep03652.

Authors

Emiko Aomatsu¹, Noriko Takahashi², Shunsuke Sawada³, Naoto Okubo⁴, Tomokazu Hasegawa⁵, Masayuki Taira⁶, Hiroyuki Miura⁷, Akira Ishisaki², Naoyuki Chosa²

Affiliations

¹ 1] Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Yahaba, Iwate 028-3694, Japan [2] Division of Orthodontics, Department of Developmental Oral Health Science, Iwate Medical University School of Dentistry, Morioka, Iwate 020-8505, Japan.
² Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Yahaba, Iwate 028-3694, Japan.
³ 1] Division of Periodontology, Department of Conservative Dentistry, Iwate Medical University School of Dentistry, Morioka, Iwate 020-8505, Japan [2] Clinical Research Laboratory, Iwate Medical University School of Dentistry, Morioka, Iwate 020-8505, Japan.
⁴ 1] Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Yahaba, Iwate 028-3694, Japan [2].
⁵ Department of Pediatric Dentistry, Tokushima University Hospital, Tokushima 770-8504, Japan.
⁶ Department of Biomedical Engineering, Iwate Medical University, Yahaba, Iwate 028-3694, Japan.
⁷ Division of Orthodontics, Department of Developmental Oral Health Science, Iwate Medical University School of Dentistry, Morioka, Iwate 020-8505, Japan.

Abstract

Human mesenchymal stem cells (hMSCs) remodel or regenerate various tissues through several mechanisms. Here, we identified the hMSC-secreted protein SCRG1 and its receptor BST1 as a positive regulator of self-renewal, migration, and osteogenic differentiation. SCRG1 and BST1 gene expression decreased during osteogenic differentiation of hMSCs. Intriguingly, SCRG1 maintained stem cell marker expression (Oct-4 and CD271/LNGFR) and the potentials of self-renewal, migration, and osteogenic differentiation, even at high passage numbers. Thus, the novel SCRG1/BST1 axis determines the fate of hMSCs by regulating their kinetic and differentiation potentials. Our findings provide a new perspective on methods for ex vivo expansion of hMSCs that maintain native stem cell potentials for bone-forming cell therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ADP-ribosyl Cyclase / genetics*
ADP-ribosyl Cyclase / metabolism
Antigens, CD / genetics*
Antigens, CD / metabolism
Cell Differentiation / genetics*
Cell Movement / genetics
Down-Regulation
Extracellular Signal-Regulated MAP Kinases / metabolism
Focal Adhesion Protein-Tyrosine Kinases / metabolism
GPI-Linked Proteins / genetics
GPI-Linked Proteins / metabolism
Gene Expression Regulation, Developmental
Humans
JNK Mitogen-Activated Protein Kinases / metabolism
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / metabolism*
Nerve Tissue Proteins / genetics*
Nerve Tissue Proteins / metabolism
Osteogenesis / genetics*
Phosphatidylinositol 3-Kinases / metabolism
Protein Binding
Protein Biosynthesis
Signal Transduction

Substances

Antigens, CD
GPI-Linked Proteins
Nerve Tissue Proteins
SCRG1 protein, human
Phosphatidylinositol 3-Kinases
Focal Adhesion Protein-Tyrosine Kinases
Extracellular Signal-Regulated MAP Kinases
JNK Mitogen-Activated Protein Kinases
ADP-ribosyl Cyclase
ADP-ribosyl cyclase 2