关键词: SDF-1/CXCR, 椎间盘退变, 退变髓核细胞, Akt, NF-κB

Abstract: Objective To investigate the role of SDFI-1/CXCR4 axis on the apoptosis of human degenerative nucleus pulposus cells (NPCs) and its potential molecular mechanism. Methods The intervertebral disces tissues from clinical discectomy were divided into normal group and intervertebral disc degeneration (IVD) group according to Pfirrmann classification. The different expressions of SDF 1 and CXCR4 in human IVDs were tested by immunohistochemistry, quantify polymerase chain reaction (q-PCR) and Western blot. The primary degenerative NPCs were primary cultured. The generationⅢ～ⅤNPCs were treated with 10ng/ml SDF-1, in the presence of or in the absence of CXCR4 siRNA transfection and 20μM NF-κB inhibitor (pyrrolidine dithiocar bamate , PDTC). The transfection efficiency and target protein of signal pathway were verified by Western blot, the apoptosis of NPCs were tested by Annexin V/PI, the nucleus transferlocation of P65 from NF-κB were tested by immunofluorescent method. ResultsSDF-1and CXCR4 were both expressed in all donor tissues, however, there was a significantly increased in the degenerative IVDs. The apoptosis of degenerative NPCs were expedited by SDF-1 stimulation, which was significantly suppressed by CXCR4 silencing by siRNA (P<0.05). Furthermore, with SDF-1 stimulation, the expressions of phosphorylated P65 was significantly increased and the P65 perssad transferred to the nucleuses, which could be suppressed by the NF-κB inhibitor, PDTC(P﹤0.05). ConclusionsThe expression levels of SDF-1 and CXCR4 were increased in degenerative NP tissue. The SDF/CXCR4 axis is considered to induce apoptotic of human degenerative NPCs via the NF-κB signaling pathway.

Key words: SDF-1/CXCR4, intervertebral disc degeneration, degenerative nucleus pulposus cells, Akt, NF-κB