AIMS: 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). MAIN METHODS: To mediate ICAT overexpression in hASC, we used a lentiviral gene transfer technique. We further determined the role of ICAT by RNAi technique. KEY FINDINGS: 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. SIGNIFICANCE: Taken together, these findings indicated that ICAT participated in regulating hASC proliferation and differentiation by modulating Wnt signaling.
AIMS: 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). MAIN METHODS: To mediate ICAT overexpression in hASC, we used a lentiviral gene transfer technique. We further determined the role of ICAT by RNAi technique. KEY FINDINGS: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. SIGNIFICANCE: Taken together, these findings indicated that ICAT participated in regulating hASC proliferation and differentiation by modulating Wnt signaling.
Authors: Rongrong Zhang; Babatunde O Oyajobi; Stephen E Harris; Di Chen; Christopher Tsao; Hong-Wen Deng; Ming Zhao Journal: Bone Date: 2012-09-29 Impact factor: 4.398
Authors: Sébastien Foulquier; Evangelos P Daskalopoulos; Gentian Lluri; Kevin C M Hermans; Arjun Deb; W Matthijs Blankesteijn Journal: Pharmacol Rev Date: 2018-01 Impact factor: 25.468