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生物硅对人成骨样细胞护骨素/RANKL 比值的作用。

The role of biosilica in the osteoprotegerin/RANKL ratio in human osteoblast-like cells.

机构信息

Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.

出版信息

Biomaterials. 2010 Oct;31(30):7716-25. doi: 10.1016/j.biomaterials.2010.07.002. Epub 2010 Jul 29.

Abstract

Earlier studies have demonstrated that biosilica, synthesized by the enzyme silicatein, induces hydroxyapatite formation in osteoblast-like SaOS-2 cells. Here we study the effect of biosilica on the expressions of osteoprotegerin [OPG] and the receptor activator for NF-kappaB ligand [RANKL] in the SaOS-2 cell model. We show that during growth of SaOS-2 cells on biosiliceous matrices hydroxyapatite formation is induced, while syntheses of cartilaginous proteoglycans and sulfated glycosaminoglycans are down-regulated. Furthermore, quantitative real-time RT-PCR analysis revealed a strong time-depended increase in expression of OPG in biosilica exposed SaOS-2 cells while the steady-state expression level of RANKL remained unchanged. These results have been corroborated on the protein level by ELISA assays. Therefore, we propose that biosilica stimulated OPG synthesis in osteoblast-like cells counteracts those pathways that control RANKL expression and function (e.g. maturation of pre-osteoclasts and activation of osteoclasts). Hence, the data obtained in the present study reveal the considerable biomedical potential of biosilica for treatment and prophylaxis of osteoporotic disorders.

摘要

早期研究表明,酶硅酸盐合成的生物硅会诱导成骨样 SaOS-2 细胞形成羟磷灰石。在这里,我们研究了生物硅对 SaOS-2 细胞模型中护骨素 [OPG] 和核因子-κB 受体激活剂配体 [RANKL] 的表达的影响。我们发现,在 SaOS-2 细胞生长在生物硅基质上时,会诱导羟磷灰石的形成,而软骨蛋白聚糖和硫酸化糖胺聚糖的合成则受到抑制。此外,定量实时 RT-PCR 分析显示,在暴露于生物硅的 SaOS-2 细胞中,OPG 的表达随着时间的推移而强烈增加,而 RANKL 的稳定表达水平保持不变。这些结果在蛋白水平上通过 ELISA 检测得到了证实。因此,我们提出生物硅刺激成骨样细胞中 OPG 的合成,从而抵消了那些控制 RANKL 表达和功能的途径(例如,破骨细胞前体的成熟和破骨细胞的激活)。因此,本研究获得的数据揭示了生物硅在治疗和预防骨质疏松症方面的巨大的生物医学潜力。

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