ICAT participates in proliferation and osteogenic differentiation of human adipose tissue-derived mesenchymal stem cell.
OBJECTIVE
The Wnt/beta-catenin pathway plays a critical part in several cell physiology events associated with embryonic development and adult homeostasis, including determination, proliferation, migration, and differentiation. However, the role of Wnt signaling in osteoblastogenesis from mesenchymal stem cells (MSC) remains a controversial matter. Therefore, in the present study, we investigated how ICAT (inhibitor of beta-catenin and TCF-4), a negative regulator of the Wnt signaling pathway, influenced differentiation and proliferation of human adipose tissue-derived stromal cells (hASC).


METHODS
To mediate ICAT overexpression in hASC, we used a lentiviral gene transfer technique. We further determined the role of ICAT by RNAi technique.


RESULTS
ICAT-transduced hASC exhibited lower TCF promoter activity and cellular growth capacity than control cells, but ICAT overexpression did not affect hASC attachment efficiency. ICAT overexpression also increased osteogenic differentiation. Conversely, introduction of an ICAT siRNA oligonucleotide increased TCF promoter activity and cellular proliferation, but it inhibited osteogenic differentiation.


CONCLUSIONS
Taken together, these findings indicated that ICAT participated in regulating hASC proliferation and differentiation by modulating Wnt signaling.
Kim
Yeon Jeong
YJ
Department of Physiology, School of Medicine, Pusan National University, Pusan, Republic of Korea.
Kim
Jong Tae
JT
Bae
Yong Chan
YC
Suh
Kuen Taek
KT
Jung
Jin Sup
JS
D048868:Adaptor Proteins, Signal Transducing; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000328:Adult; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D016086:Lentivirus / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D010012:Osteogenesis / Q000502:physiology*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051153:Wnt Proteins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C411982:CTNNBIP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D051153:Wnt Proteins