Wei Zhun, Li Hao-Huan
Department of Orthopedics, Central Laboratory, Renmin Hospital of Wuhan University Wuhan, Hubei Province, China.
Department of Orthopedics, Renmin Hospital of Wuhan University Wuhan, Hubei Province, China.
Int J Clin Exp Pathol. 2015 Dec 1;8(12):15599-610. eCollection 2015.
Osteoarthritis is not an uncommon disease worldwide and it is characterized by chondrocytes apoptosis in articular cartilages. Previous researches had discovered that insulin-like growth factor binding protein-3 (IGFBP-3) was abundant inside the osteoarthritic cartilages and the more IGFBP-3, the worse of osteoarthritis. However, there is still little knowledge of the association between the onset of osteoarthritis and the yield of IGFBP-3 in cartilages. In consideration of the apoptotic effect of IGFBP-3 on other types of cells, we had hypothesized that IGFBP-3 may induce the chondrocytes apoptosis, which was highly considered as the origin of the osteoarthritis. Exposing the cultured chondrocytes to exogenous recombinant IGFBP-3, we were able to observed the apoptotic chondrocytes under microscope and figured out an increased proportion (P<0.05) of them by both CCK-8 assay and flow cytometry. Under laser confocal microscope, we also found that the apoptosis of chondrocytes induced by IGFBP-3 were committed to the nucleus-mitochondria translocation of Nur77, which is nuclear protein, and this phenomena was similar as the one described in malignant cells only. In conclusion, our work suggested that IGFBP-3 may trigger osteoarthritis by inducing the chondrocytes apoptotic through nucleus-mitochondria translocation of Nur77.
骨关节炎在全球范围内并非罕见疾病,其特征是关节软骨中的软骨细胞凋亡。先前的研究发现,胰岛素样生长因子结合蛋白-3(IGFBP-3)在骨关节炎软骨中含量丰富,且IGFBP-3含量越高,骨关节炎病情越严重。然而,对于骨关节炎的发病与软骨中IGFBP-3产生之间的关联仍知之甚少。考虑到IGFBP-3对其他类型细胞的凋亡作用,我们曾推测IGFBP-3可能诱导软骨细胞凋亡,而软骨细胞凋亡被高度认为是骨关节炎的起源。将培养的软骨细胞暴露于外源性重组IGFBP-3后,我们能够在显微镜下观察到凋亡的软骨细胞,并通过CCK-8测定法和流式细胞术得出其比例增加(P<0.05)。在激光共聚焦显微镜下,我们还发现IGFBP-3诱导的软骨细胞凋亡与核蛋白Nur77从细胞核向线粒体的转位有关,而这种现象仅在恶性细胞中出现过。总之,我们的研究表明,IGFBP-3可能通过Nur77从细胞核向线粒体的转位诱导软骨细胞凋亡,从而引发骨关节炎。