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

doi:10.1016/j.cellsig.2015.09.004

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

Department of Biochemistry

Research output: Contribution to journal › Article › peer-review

9 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 language	English
Pages (from-to)	2389-2400
Number of pages	12
Journal	Cellular Signalling
Volume	27
Issue number	12
DOIs	https://doi.org/10.1016/j.cellsig.2015.09.004
Publication status	Published - 2015 Dec 1

Bibliographical note

Funding Information:
This work was supported by the grants ( NRF-2012M3A9A9055078 ; NRF-2008-0062422 ; 2015 K000180 ) funded by the Korean Ministry of Science, ICT and Future Planning , and the grant R01-GM041890 funded by NIH , USA.

Publisher Copyright:
© 2015 Elsevier Inc.

All Science Journal Classification (ASJC) codes

Cell Biology

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10.1016/j.cellsig.2015.09.004

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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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note = "Funding Information: This work was supported by the grants ( NRF-2012M3A9A9055078 ; NRF-2008-0062422 ; 2015 K000180 ) funded by the Korean Ministry of Science, ICT and Future Planning , and the grant R01-GM041890 funded by NIH , USA. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

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AU - Kim, Dae Won

N1 - Funding Information: This work was supported by the grants ( NRF-2012M3A9A9055078 ; NRF-2008-0062422 ; 2015 K000180 ) funded by the Korean Ministry of Science, ICT and Future Planning , and the grant R01-GM041890 funded by NIH , USA. Publisher Copyright: © 2015 Elsevier Inc.

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N2 - 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

Abstract

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