Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification or the posterior longitudinal ligament
Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification or the posterior longitudinal ligament
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DOI：
10.1007/s00223-002-0021-1
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发表时间：
2004-05-01
影响因子：
4.2
通讯作者：
Motomura, S
中科院分区：
文献类型：
--
作者：
Iwasaki, K;Furukawa, KI;Motomura, S
脊柱后纵韧带骨化（OPLL）的特征是脊柱韧带内异位骨形成。作用于后部韧带的机械应力被认为是OPLL进展的重要因素。为了阐明这一机制，我们研究了体外周期性拉伸（120%峰到峰，在0.5 Hz）对来自OPLL（OPLL细胞）和非OPLL（非OPLL细胞）患者的培养脊髓韧带细胞的影响。在OPLL细胞中，Cbfal（成骨细胞特异性转录因子）、I型胶原、碱性磷酸酶（ALP）、骨钙素和整合素β 1（机械传感器）的mRNA表达通过周期性拉伸而增加，而在非OPLL细胞中未观察到变化。周期性拉伸对来自OPLL和非OPLL患者的脊柱韧带组织的影响也通过使用针对Cbfal的抗体的免疫组织化学进行分析。在OPLL患者的脊柱韧带组织中心，通过周期性牵拉，Cbfal的表达增加。而在非OPLL患者的组织中没有观察到变化。此外。MAPK激酶（MEK）特异性抑制剂U0126可抑制牵张诱导的OPLL细胞Cbfa1、ALP和I型胶原mRNA的表达。这些结果表明，在OPLL细胞中，机械应力被整合素β 1转化为细胞内信号，Cbfal通过MAP激酶途径被激活。因此，我们认为机械应力通过增加Cbfal表达在OPLL的进展中起着关键作用。
Ossification of the posterior longitudinal ligament of the spine (OPLL) is characterized by ectopic bone formation in the spinal ligaments. Mechanical stress, which acts on the posterior ligaments, is thought to be an important factor in the progression of OPLL. To clarify this mechanism, we investigated the effects of in vitro cyclic stretch (120% peak to peak, at 0.5 Hz) on cultured spinal ligament cells derived from OPLL (OPLL cells) and non-OPLL (non-OPLL cells) patients. The rnRNA expressions of Cbfal (an osteoblast-specific transcription factor), type I collagen, alkaline phosphatase (ALP), osteocalcin and integrin beta1 (a mechanotransducer) were increased by cyclic stretch in OPLL cells, whereas no change was observed in non-OPLL cells. The effects of cyclic stretch on the spinal ligament tissues derived from OPLL and non-OPLL patients were also analyzed by immunohistochemistry using an antibody against Cbfal. The expression of Cbfal was increased by cyclic stretch at the center of the spinal ligament tissues of OPLL patients. whereas no change was observed in the tissues of non-OPLL patients. Furthermore. U0126, a specific inhibitor of MAPK kinase (MEK), suppressed the stretch-induced mRNA expressions of Cbfa1, ALP and type I collagen in OPLL cells. These results suggest that in OPLL cells, mechanical stress is converted by integrin beta1 into intracellular signaling and that Cbfal is activated through the MAP kinase pathway. Therefore, we propose that mechanical stress plays a key role in the progression of OPLL through an increase in Cbfal expression.