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首页> 外文期刊>Journal of orthopaedic research >Exogenous and autocrine growth factors stimulate human intervertebral disc cell proliferation via the ERK and Akt pathways
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Exogenous and autocrine growth factors stimulate human intervertebral disc cell proliferation via the ERK and Akt pathways

机译:外源性和自分泌生长因子通过ERK和Akt途径刺激人椎间盘细胞增殖

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摘要

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.
机译:椎间盘(IVD)变性伴有生长因子过表达和细胞增殖增加,可能代表了组织修复过程。因此,我们研究了外源和自分泌生长因子对人IVD细胞增殖的影响。我们观察到,血小板衍生生长因子(PDGF),碱性成纤维细胞生长因子(bFGF)和胰岛素样生长因子I(IGF-1)通过激活MEK / ERK和DNA刺激人IVD细胞的DNA合成。 PI-3K / Akt信号转导途径。此外,受IVD细胞调节的培养基(CM)在同一细胞中诱导DNA合成,表明分泌了自分泌生长因子。 CM也诱导了MEK / ERK和PI-3K / Akt途径,而它们的抑制作用在很大程度上逆转了CM对DNA合成的诱导。这些对外源和自分泌生长因子的反应在髓核(NP)和纤维环(AF)细胞培养物中在质量上都相似。人体活组织检查中的免疫组织化学研究表明,两种信号通路均得到了显着激活,这在增殖细胞群中最为明显。这些体外和体内数据表明,人IVD细胞的增殖主要通过MEK / ERK和PI-3K / Akt途径受到外源和自分泌生长因子的调控。这可能有助于未来干预方法的设计。

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