Suppression of Nkx3.2 by phosphatidylinositol-3-kinase signaling regulates cartilage development by modulating chondrocyte hypertrophy

Jeong Ah Kim, Suhjean Im, Lewis C. Cantley, Dae-Won Kim

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Phosphatidylinositol-3-kinase (PI3K) is a key regulator of diverse biological processes including cell proliferation, migration, survival, and differentiation. While a role of PI3K in chondrocyte differentiation has been suggested, its precise mechanisms of action are poorly understood. Here we show that PI3K signaling can down-regulate Nkx3.2 at both mRNA and protein levels in various chondrocyte cultures in vitro. In addition, we have intriguingly found that p85β, not p85α, is specifically employed as a regulatory subunit for PI3K-mediated Nkx3.2 suppression. Furthermore, we found that regulation of Nkx3.2 by PI3K requires Rac1-PAK1, but not Akt, signaling downstream of PI3K. Finally, using embryonic limb bud cultures, ex vivo long bone cultures, and p85β knockout mice, we demonstrated that PI3K-mediated suppression of Nkx3.2 in chondrocytes plays a role in the control of cartilage hypertrophy during skeletal development in vertebrates.

Original languageEnglish
Pages (from-to)2389-2400
Number of pages12
JournalCellular Signalling
Volume27
Issue number12
DOIs
Publication statusPublished - 2015 Dec 1

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Phosphatidylinositol 3-Kinase
Chondrocytes
Hypertrophy
Cartilage
Biological Phenomena
Limb Buds
Knockout Mice
Cell Movement
Vertebrates
Down-Regulation
Cell Proliferation
Bone and Bones
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

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title = "Suppression of Nkx3.2 by phosphatidylinositol-3-kinase signaling regulates cartilage development by modulating chondrocyte hypertrophy",
abstract = "Phosphatidylinositol-3-kinase (PI3K) is a key regulator of diverse biological processes including cell proliferation, migration, survival, and differentiation. While a role of PI3K in chondrocyte differentiation has been suggested, its precise mechanisms of action are poorly understood. Here we show that PI3K signaling can down-regulate Nkx3.2 at both mRNA and protein levels in various chondrocyte cultures in vitro. In addition, we have intriguingly found that p85β, not p85α, is specifically employed as a regulatory subunit for PI3K-mediated Nkx3.2 suppression. Furthermore, we found that regulation of Nkx3.2 by PI3K requires Rac1-PAK1, but not Akt, signaling downstream of PI3K. Finally, using embryonic limb bud cultures, ex vivo long bone cultures, and p85β knockout mice, we demonstrated that PI3K-mediated suppression of Nkx3.2 in chondrocytes plays a role in the control of cartilage hypertrophy during skeletal development in vertebrates.",
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Suppression of Nkx3.2 by phosphatidylinositol-3-kinase signaling regulates cartilage development by modulating chondrocyte hypertrophy. / Kim, Jeong Ah; Im, Suhjean; Cantley, Lewis C.; Kim, Dae-Won.

In: Cellular Signalling, Vol. 27, No. 12, 01.12.2015, p. 2389-2400.

Research output: Contribution to journalArticle

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