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Updated: Jul 3, 2026

Chondrogenic Pellet Formation from Cord Blood-derived Induced Pluripotent Stem Cells
Published on: June 19, 2017
IGF2-driven PI3 kinase and TGFbeta signaling pathways in chondrogenesis
Kazunori Hamamura1, Ping Zhang, Hiroki Yokota
1Department of Biomedical Engineering, Indiana University - Purdue University Indianapolis, Indianapolis, IN 46202, USA.
Abstract:
Insulin-like growth factor-2 (IGF2) is essential for fetal development as well as maintenance of adult organs such as brain and liver. Although genetic polymorphisms of IGF2 are linked to cytoskeletal variations little is known about the mechanisms of IGF2 action in proliferation and differentiation of chondrocytes for skeletal growth. A genome-wide mRNA expression analysis using C28/I2 chondrocyte cells studied potential signaling pathways underlying the responses to IGF2. Microarray data predicted involvement of the phosphatidylinositol 3-kinase (PI3K) and transforming growth factor beta (TGFbeta) signaling pathways. Protein analyses revealed IGF2 administration activated phosphorylation of Akt and GSK3beta in the PI3K pathway. LY294002 (selective inhibitor of PI3K) blocked Akt phosphorylation and abolished IGF2-driven elevation of the mRNA levels of the proteoglycans, Aggrecan and Versican. LY294002 did not suppress upregulation of TGFbeta mRNA induced by IGF2, so IGF2 activates PI3K and TGFbeta pathways. IGF2-driven transcriptional activation of proteoglycan genes such as Aggrecan and Versican is mediated by the PI3K pathway.
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