PDF(Pubmed)
Abstract：
Sensory nerves play a crucial role in maintaining bone homeostasis by releasing Semaphorin 3A (Sema3A). However, the specific mechanism of Sema3A in regulation of bone marrow mesenchymal stem cells (BMMSCs) during bone remodelling remains unclear. The tibial denervation model was used and the denervated tibia exhibited significantly lower mass as compared to sham operated bones. In vitro, BMMSCs cocultured with dorsal root ganglion cells (DRGs) or stimulated by Sema3A could promote osteogenic differentiation through the Wnt/β-catenin/Nrp1 positive feedback loop, and the enhancement of osteogenic activity could be inhibited by SM345431 (Sema3A-specific inhibitor). In addition, Sema3A-stimulated BMMSCs or intravenous injection of Sema3A could promote new bone formation in vivo. To sum up, the coregulation of bone remodelling is due to the ageing of BMMSCs and increased osteoclast activity. Furthermore, the sensory neurotransmitter Sema3A promotes osteogenic differentiation of BMMSCs via Wnt/β-catenin/Nrp1 positive feedback loop, thus promoting osteogenesis in vivo and in vitro.
摘要：
感觉神经通过释放信号蛋白3A（Sema3A）在维持骨稳态中起关键作用。然而,Sema3A在骨重建过程中调节骨髓间充质干细胞（BMMSCs）的具体机制尚不清楚。使用胫骨去神经支配模型，与假手术骨相比，去神经支配的胫骨显示出明显较低的质量。体外，与背根神经节细胞（DRGs）共培养或Sema3A刺激的BMMSCs可通过Wnt/β-catenin/Nrp1正反馈回路促进成骨分化，SM345431（Sema3A特异性抑制剂）可以抑制成骨活性的增强。此外,Sema3A刺激的BMMSCs或静脉注射Sema3A可以促进体内新骨形成。总而言之,骨重建的共同调节是由于BMMSCs的老化和破骨细胞活性的增加。此外，感觉神经递质Sema3A通过Wnt/β-catenin/Nrp1正反馈环促进BMMSCs成骨分化,从而促进体内和体外成骨。
