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Akt regulates skeletal development through GSK3, mTOR, and FoxOs

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Title: Akt regulates skeletal development through GSK3, mTOR, and FoxOs
Authors: Rokutanda, Satoshi / Fujita, Takashi / Kanatani, Naoko / Yoshida, Carolina A. / Komori, Hisato / Liu, Wenguang / Mizuno, Akio / Komori, Toshihisa
Issue Date: 1-Apr-2009
Publisher: Elsevier
Citation: Developmental Biology, 328(1), pp.78-93; 2009
Abstract: Although Akt plays key roles in various cellular processes, the functions of Akt and Akt downstream signaling pathways in the cellular processes of skeletal development remain to be clarified. By analyzing transgenic embryos that expressed constitutively active Akt (myrAkt) or dominant-negative Akt in chondrocytes, we found that Akt positively regulated the four processes of chondrocyte maturation, chondrocyte proliferation, cartilage matrix production, and cell growth in skeletal development. As phosphorylation of GSK3β, S6K, and FoxO3a was enhanced in the growth plates of myrAkt transgenic mice, we examined the Akt downstream signaling pathways by organ culture. The Akt-mTOR pathway was responsible for positive regulation of the four cellular processes. The Akt-FoxO pathway enhanced chondrocyte proliferation but inhibited chondrocyte maturation and cartilage matrix production, while the Akt-GSK3 pathway negatively regulated three of the cellular processes in limb skeletons but not in vertebrae due to less GSK3 expression in vertebrae. These findings indicate that Akt positively regulates the cellular processes of skeletal growth and endochondral ossification, that the Akt-mTOR, Akt-FoxO, and Akt-GSK3 pathways positively or negatively regulate the cellular processes, and that Akt exerts its function in skeletal development by tuning the three pathways in a manner dependent on the skeletal part.
Keywords: Akt / Cartilage matrix / Cell growth / Chondrocyte maturation / Chondrocyte proliferation / FoxO / GSK3 / mTOR / Skeletal development / Transgenic mouse
URI: http://hdl.handle.net/10069/21352
ISSN: 00121606
DOI: 10.1016/j.ydbio.2009.01.009
Rights: Copyright (c) 2009 Elsevier Inc. All rights reserved.
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/21352

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