title: Exogenous and autocrine growth factors stimulate human intervertebral disc cell proliferation via the ERK and Akt pathways.
abstract: 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.
authors: Laboratory of Cell Proliferation and Ageing, Institute of Biology, NCSR Demokritos, 153 10 Athens, Greece.
authors: Harris
authors: H
authors: Pratsinis
authors: Vasos
authors: V
authors: Constantinou
authors: Kitty
authors: K
authors: Pavlakis
authors: George
authors: G
authors: Sapkas
authors: Dimitris
authors: D
authors: Kletsas
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007403:Intervertebral Disc / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases