Kim Yeon Jeong, Kim Jong Tae, Bae Yong Chan, Suh Kuen Taek, Jung Jin Sup
Department of Physiology, School of Medicine, Pusan National University, Pusan, Republic of Korea.
Life Sci. 2008 Dec 19;83(25-26):851-8. doi: 10.1016/j.lfs.2008.09.030. Epub 2008 Oct 22.
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).
To mediate ICAT overexpression in hASC, we used a lentiviral gene transfer technique. We further determined the role of ICAT by RNAi technique.
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.
Taken together, these findings indicated that ICAT participated in regulating hASC proliferation and differentiation by modulating Wnt signaling.
Wnt/β-连环蛋白信号通路在与胚胎发育和成人内环境稳定相关的多个细胞生理事件中起关键作用，包括细胞命运决定、增殖、迁移和分化。然而，Wnt信号在间充质干细胞（MSC）向成骨细胞分化过程中的作用仍存在争议。因此，在本研究中，我们探究了Wnt信号通路的负调节因子ICAT（β-连环蛋白和TCF-4的抑制剂）如何影响人脂肪组织来源的基质细胞（hASC）的分化和增殖。
为了在hASC中介导ICAT的过表达，我们使用了慢病毒基因转移技术。我们还通过RNAi技术进一步确定了ICAT的作用。
与对照细胞相比，转导ICAT的hASC表现出较低的TCF启动子活性和细胞生长能力，但ICAT的过表达不影响hASC的贴壁效率。ICAT的过表达也增加了成骨分化。相反，引入ICAT siRNA寡核苷酸增加了TCF启动子活性和细胞增殖，但抑制了成骨分化。
综上所述，这些发现表明ICAT通过调节Wnt信号参与调控hASC的增殖和分化。
