Leptin Induces Cyclin D1 Expression and Proliferation of Human Nucleus Pulposus Cells via JAK/STAT, PI3K/Akt and MEK/ERK Pathways

Leptin Induces Cyclin D1 Expression and Proliferation of Human Nucleus Pulposus Cells via JAK/STAT, PI3K/Akt and MEK/ERK Pathways

Increasing evidence suggests that obesity and aberrant proliferation of nucleus pulposus (NP) cells are associated with intervertebral disc degeneration. Leptin, a hormone with increased circulating level in obesity, has been shown to stimulate cell proliferation in a tissue-dependent manner. Nevert...

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Main Authors: Li, Zheng, Shen, Jianxiong, Wu, William Ka Kei, Yu, Xin, Liang, Jinqian, Qiu, Guixing, Liu, Jiaming
Format: Online
Language:English
Published: Public Library of Science 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534060/
id pubmed-3534060
recordtype oai_dc
spelling pubmed-35340602013-01-08 Leptin Induces Cyclin D1 Expression and Proliferation of Human Nucleus Pulposus Cells via JAK/STAT, PI3K/Akt and MEK/ERK Pathways Li, Zheng Shen, Jianxiong Wu, William Ka Kei Yu, Xin Liang, Jinqian Qiu, Guixing Liu, Jiaming Research Article Increasing evidence suggests that obesity and aberrant proliferation of nucleus pulposus (NP) cells are associated with intervertebral disc degeneration. Leptin, a hormone with increased circulating level in obesity, has been shown to stimulate cell proliferation in a tissue-dependent manner. Nevertheless, the effect of leptin on the proliferation of human NP cells has not yet been demonstrated. Here, we show that leptin induced the proliferation of primary cultured human NP cells, which expressed the leptin receptors OBRa and OBRb. Induction of NP cell proliferation was confirmed by CCK8 assay and immunocytochemistry and Real-time PCR for PCNA and Ki-67. Mechanistically, leptin induced the phosphorylation of STAT3, Akt and ERK1/2 accompanied by the upregulation of cyclin D1. Pharmacological inhibition of JAK/STAT3, PI3K/Akt or MEK/ERK signaling by AG490, Wortmannin or U0126, respectively, reduced leptin-induced cyclin D1 expression and NP cell proliferation. These experiments also revealed an intricate crosstalk among these signaling pathways in mediating the action of leptin. Taken together, we show that leptin induces human NP cell cyclin D1 expression and proliferation via activation of JAK/STAT3, PI3K/Akt or MEK/ERK signaling. Our findings may provide a novel molecular mechanism that explains the association between obesity and intervertebral disc degeneration. Public Library of Science 2012-12-31 /pmc/articles/PMC3534060/ /pubmed/23300886 http://dx.doi.org/10.1371/journal.pone.0053176 Text en © 2012 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Li, Zheng
Shen, Jianxiong
Wu, William Ka Kei
Yu, Xin
Liang, Jinqian
Qiu, Guixing
Liu, Jiaming
spellingShingle Li, Zheng
Shen, Jianxiong
Wu, William Ka Kei
Yu, Xin
Liang, Jinqian
Qiu, Guixing
Liu, Jiaming
Leptin Induces Cyclin D1 Expression and Proliferation of Human Nucleus Pulposus Cells via JAK/STAT, PI3K/Akt and MEK/ERK Pathways
author_facet Li, Zheng
Shen, Jianxiong
Wu, William Ka Kei
Yu, Xin
Liang, Jinqian
Qiu, Guixing
Liu, Jiaming
author_sort Li, Zheng
title Leptin Induces Cyclin D1 Expression and Proliferation of Human Nucleus Pulposus Cells via JAK/STAT, PI3K/Akt and MEK/ERK Pathways
title_short Leptin Induces Cyclin D1 Expression and Proliferation of Human Nucleus Pulposus Cells via JAK/STAT, PI3K/Akt and MEK/ERK Pathways
title_full Leptin Induces Cyclin D1 Expression and Proliferation of Human Nucleus Pulposus Cells via JAK/STAT, PI3K/Akt and MEK/ERK Pathways
title_fullStr Leptin Induces Cyclin D1 Expression and Proliferation of Human Nucleus Pulposus Cells via JAK/STAT, PI3K/Akt and MEK/ERK Pathways
title_full_unstemmed Leptin Induces Cyclin D1 Expression and Proliferation of Human Nucleus Pulposus Cells via JAK/STAT, PI3K/Akt and MEK/ERK Pathways
title_sort leptin induces cyclin d1 expression and proliferation of human nucleus pulposus cells via jak/stat, pi3k/akt and mek/erk pathways
description Increasing evidence suggests that obesity and aberrant proliferation of nucleus pulposus (NP) cells are associated with intervertebral disc degeneration. Leptin, a hormone with increased circulating level in obesity, has been shown to stimulate cell proliferation in a tissue-dependent manner. Nevertheless, the effect of leptin on the proliferation of human NP cells has not yet been demonstrated. Here, we show that leptin induced the proliferation of primary cultured human NP cells, which expressed the leptin receptors OBRa and OBRb. Induction of NP cell proliferation was confirmed by CCK8 assay and immunocytochemistry and Real-time PCR for PCNA and Ki-67. Mechanistically, leptin induced the phosphorylation of STAT3, Akt and ERK1/2 accompanied by the upregulation of cyclin D1. Pharmacological inhibition of JAK/STAT3, PI3K/Akt or MEK/ERK signaling by AG490, Wortmannin or U0126, respectively, reduced leptin-induced cyclin D1 expression and NP cell proliferation. These experiments also revealed an intricate crosstalk among these signaling pathways in mediating the action of leptin. Taken together, we show that leptin induces human NP cell cyclin D1 expression and proliferation via activation of JAK/STAT3, PI3K/Akt or MEK/ERK signaling. Our findings may provide a novel molecular mechanism that explains the association between obesity and intervertebral disc degeneration.
publisher Public Library of Science
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534060/
_version_ 1611943903846465536

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