Peripheral nerve‐derived Sema3A promotes osteogenic differentiation of mesenchymal stem cells through the Wnt/β‐catenin/Nrp1 positive feedback loop

Author:

Shi Jingcun123,Zhang Bingqing123,Wu Ziqian123,Zhang Yuhan123,Gupta Anand4,Wang Xudong5,Wang Jieyu123,Pan Lisha236,Xiao Meng123,Zhang Shijian123,Wang Lei1237ORCID

Affiliation:

1. Department of Oral and Maxillofacial Surgery – Head & Neck Oncology Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai China

2. College of Stomatology Shanghai Jiao Tong University Shanghai China

3. National Center for Stomatology National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology Shanghai China

4. Department of Dentistry, Oral Health Centre Government Medical College Hospital Chandigarh India

5. Department of Stomatology Shanghai East Hospital, School of Medicine, Tongji University Shanghai China

6. Department of Prosthodontics Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai China

7. Department of Stomatology Fengcheng Hospital Shanghai China

Abstract

AbstractSensory 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.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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