Open AccessA study of Drynaria fortunei in modulation of BMP–2 signalling by bone tissue engineering
Author(s) -
Guo-Chung Dong,
Tzn Yuan,
Chi Han Li,
Chih Ying,
Chao Ming Su,
Ching-Lien Huang,
YanHsiung Wang,
Tzer-Min Lee
Publication year - 2020
Publication title -
turkish journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.277
H-Index - 27
eISSN - 1303-6165
pISSN - 1300-0144
DOI - 10.3906/sag-2001-148
Subject(s) - naringin , smad , microbiology and biotechnology , mesenchymal stem cell , biomedical engineering , medicine , signal transduction , chemistry , biology , chromatography
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. Materials and methods 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, C 2 C 12 , 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.Results 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. Conclusion 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.