IFITM1 increases osteogenesis through Runx2 in human alveolar-derived bone marrow stromal cells.
The exact molecular mechanisms governing the differentiation of bone marrow stromal stem/progenitor cells (BMSCs) into osteoblasts remain largely unknown. In this study, a highly expressed protein that had a high degree of homology with interferon-induced transmembrane protein 1 (IFITM1) was identified using differentially expressed gene (DEG) screening. We sought to determine whether IFITM1 influenced osteoblast differentiation. During differentiation, IFITM1 expression gradually increased from 5 to 10days and subsequently decreased at 15 days in culture. Analysis of IFITM1 protein expression in several cell lines as well as in situ studies on human tissues revealed its selective expression in bone cells and human bone. Proliferation of human alveolar-derived bone marrow stromal cells (hAD-BMSCs) was significantly inhibited by IFITM1 knockdown by using short hairpin RNA, as were bone specific markers such as alkaline phosphatase, collagen type I α 1, bone sialoprotein, osteocalcin, and osterix were decreased. Calcium accumulation also decreased following IFITM1 knockdown. Moreover, IFITM1 knockdown in hAD-BMSCs was associated with inhibition of Runx2 mRNA and protein expression. Collectively, the present data provide evidence for the role of IFITM1 in osteoblast differentiation. The exact mechanisms of IFITM1's involvement in osteoblast differentiation are still under investigation.
Department of Periodontology, School of Dentistry, Wonkwang University, Iksan, Jeonbuk, South Korea.
Beom-Su
BS
Kim
Hyung-Jin
HJ
Kim
Jin Seong
JS
Kim
Yong-Ouk
YO
You
Homa
H
Zadeh
Hong-In
HI
Shin
Seung-Jin
SJ
Lee
Yoon-Jeong
YJ
Park
Takashi
T
Takata
Sung-Hee
SH
Pi
Jun
J
Lee
Hyung-Keun
HK
You
D000469:Alkaline Phosphatase / Q000378:metabolism; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism
D000943:Antigens, Differentiation; D015415:Biomarkers; C000716127:COL1A1 protein, human; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit; D034741:RNA, Small Interfering; C493709:RUNX2 protein, human; C062010:leu-13 antigen; D000469:Alkaline Phosphatase; D002118:Calcium