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Exogenous and autocrine growth factors stimulate human intervertebral disc cell proliferation via the ERK and Akt pathways.
MedLine Citation:
PMID:  22105580     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Intervertebral disc (IVD) degeneration is accompanied by growth factor-overexpression and increased cell proliferation, probably representing a tissue repair process. Accordingly, we studied the effect of exogenous and autocrine growth factors on the proliferation of human IVD cells. We observed that Platelet-Derived Growth Factor (PDGF), basic Fibroblast Growth Factor (bFGF), and Insulin-like Growth Factor-I (IGF-I) stimulate DNA synthesis of human IVD cells, through the activation of the MEK/ERK and the PI-3K/Akt signal transduction pathways. Furthermore, medium conditioned (CM) by IVD cells induced DNA synthesis in the same cells, indicating the secretion of autocrine growth factors. The MEK/ERK and PI-3K/Akt pathways were also induced by CM, while their inhibition reversed in large part the DNA synthesis induction by CM. These responses to the exogenous and autocrine growth factors were qualitatively similar in both nucleus pulposus (NP) and annulus fibrosus (AF) cell cultures. Immunohistochemical studies in human biopsies showed significant activation of both signaling pathways, which was most prominent in the clusters of proliferating cells. These in vitro and in vivo data indicate that the proliferation of human IVD cells is regulated by exogenous and autocrine growth factors mainly via the MEK/ERK and PI-3K/Akt pathways; this may contribute to the design of future interventional approaches. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
Authors:
Harris Pratsinis; Vasos Constantinou; Kitty Pavlakis; George Sapkas; Dimitris Kletsas
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-21
Journal Detail:
Title:  Journal of orthopaedic research : official publication of the Orthopaedic Research Society     Volume:  -     ISSN:  1554-527X     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8404726     Medline TA:  J Orthop Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Orthopaedic Research Society.
Affiliation:
Laboratory of Cell Proliferation and Ageing, Institute of Biology, NCSR "Demokritos", 153 10 Athens, Greece.
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