Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli County, Taiwan
Center for Fundamental Science, Kaohsiung Medical University Kaohsiung, Taiwan
Turk J Med Sci. 2020 Aug 26;50(5):1444-1453. doi: 10.3906/sag-2001-148.
BACKGROUND/AIM: Drynaria fortunei (Gusuibu; GSB) is a popular traditional Chinese medicine used for bone repair. An increasing number of studies have reported that GSB induces osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). These results provide insight into the application of GSB for bone tissue engineering techniques used to repair large bone defects. However, few studies have described the molecular mechanisms of GSB.
In the present study, the effects of GSB and naringin, a marker compound, on the binding of BMP-2 to BMPR and BMP-2-derived signal transduction were investigated using surface plasmon resonance (SPR) and coculturing with BMPR- expressed cell line, C2C12, respectively. Furthermore, naringin was also used to prepare naringin contained scaffolds for bone tissue engineering. The physical and chemical properties of these scaffolds were analysed using scanning electron microscopy (SEM) and highperformance liquid chromatography (HPLC). These scaffolds were cocultured with rabbit BMSCs in vitro and implanted into rabbit calvarial defects for bone repair assessment.
The results showed that GSB and naringin affect the binding of BMP and BMPR in SPR experiments. GSB is a subtle BMP modulator that simultaneously inhibits the binding of BMP-2 to BMPR-1A and enhances its binding to BMPR-1B. In contrast, naringin inhibited BMP-2 binding to BMPR-1A. In vitro studies involving the phosphorylation of signals downstream of BMPR and Smad showed that GSB and naringin affected stem cell differentiation by inhibiting BMPR-1A signalling. When using GSB for bone tissue engineering, naringin exhibited a higher capacity for slow and gradual release from the scaffold, which promotes bone formation via osteoinduction. Moreover, control and naringin scaffolds were implanted into rabbit calvarial defects for 4 weeks, and naringin enhanced bone regeneration in vivo significantly.
GSB and its marker compound (naringin) could inhibit the binding of BMP-2 and BMPR-1A to control cell differentiation by blocked BMPR-1A signalling and enhanced BMPR-1B signalling. GSB and naringin could be good natural BMP regulators for bone tissue engineering.
背景/目的：骨碎补（Gusuibu；GSB）是一种常用的传统中药，用于促进骨修复。越来越多的研究报道，GSB 可诱导骨髓间充质干细胞（BMSCs）的成骨分化。这些结果为 GSB 应用于骨组织工程技术修复大的骨缺损提供了新的思路。然而，目前鲜有研究报道 GSB 的分子机制。
本研究采用表面等离子体共振（SPR）技术，分别以 GSB 和其特征化合物柚皮苷为研究对象，研究 GSB 和柚皮苷对 BMP-2 与 BMPR 结合以及 BMP-2 衍生信号转导的影响；同时采用 C2C12 细胞株作为 BMPR 表达细胞系，研究柚皮苷对 BMP-2 与 BMPR 结合的影响。此外，柚皮苷还被用于制备用于骨组织工程的柚皮苷载药支架。采用扫描电子显微镜（SEM）和高效液相色谱（HPLC）对支架的理化性质进行分析。体外将兔 BMSCs 与支架共培养，然后将支架植入兔颅骨缺损处，评估其促进骨修复的效果。
研究结果表明，GSB 和柚皮苷在 SPR 实验中影响 BMP 与 BMPR 的结合。GSB 是一种微妙的 BMP 调节剂，可同时抑制 BMP-2 与 BMPR-1A 的结合，增强其与 BMPR-1B 的结合。相反，柚皮苷抑制 BMP-2 与 BMPR-1A 的结合。体外研究表明，GSB 和柚皮苷通过抑制 BMPR-1A 信号通路影响信号转导下游的磷酸化，从而影响干细胞的分化。在骨组织工程中使用 GSB 时，柚皮苷可从支架中缓慢、持续释放，通过诱导成骨促进骨形成。此外，将 GSB 和柚皮苷支架分别植入兔颅骨缺损处 4 周，结果显示柚皮苷可显著增强体内骨再生。
GSB 及其特征化合物（柚皮苷）可通过阻断 BMPR-1A 信号通路和增强 BMPR-1B 信号通路，抑制 BMP-2 与 BMPR-1A 的结合，从而控制细胞分化。GSB 和柚皮苷可能是骨组织工程中良好的天然 BMP 调节剂。
Zotero 插件
