PDGF, bFGF and IGF-I stimulate the proliferation of intervertebral disc cells in vitro via the activation of the ERK and Akt signaling pathways

摘要: Intervertebral disc (IVD) degeneration is frequently characterized by increased cell proliferation, probably as a tissue regenerative response. Although many growth factors and their receptors have been shown to be expressed normally in the disc, generally over-expressed during degeneration, not all of them thoroughly studied concerning effects on IVD proliferation. In present report, three potent mitogens, platelet-derived factor (PDGF), basic fibroblast (bFGF) insulin-like factor-I (IGF-I) are examined regarding capacity induce proliferation vitro bovine coccygeal nucleus pulposus (NP) annulus fibrosus (AF) cells, well activate major intracellular signal transduction pathways. PDGF, bFGF IGF-I were found DNA synthesis quiescent cells dose-dependent manner. Maximum stimulation was induced while simultaneously exceeded only slightly that caused PDGF alone. All phosphorylate immediately extracellular-signal regulated kinases (ERKs), especially resulted sustained ERK phosphorylation. Furthermore, phosphorylation Akt both Thr308 Ser473 residues after stimulation, although bFGF-induced much weaker than provoked IGF-I. addition, MEK inhibitor PD98059 PI 3-K wortmannin block factor-induced ERK- Akt-phosphorylation, respectively, cells. Inhibition MEK/ERK or 3-K/Akt pathways significant decline proliferative cultures, simultaneous inhibition signaling abolished completely mitogenicity these factors. The above reproduced similarly NP AF cultures. Overall, results indicate stimulate via