2. Academic Validation
  3. Peripheral nerve-derived Sema3A promotes osteogenic differentiation of mesenchymal stem cells through the Wnt/β-catenin/Nrp1 positive feedback loop

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

  • J Cell Mol Med. 2024 Apr;28(8):e18201. doi: 10.1111/jcmm.18201.
Jingcun Shi 1 2 3,  Bingqing Zhang 1 2 3,  Ziqian Wu 1 2 3,  Yuhan Zhang 1 2 3,  Anand Gupta 4,  Xudong Wang 5,  Jieyu Wang 1 2 3,  Lisha Pan 2 3 6,  Meng Xiao 1 2 3,  Shijian Zhang 1 2 3,  Lei Wang 1 2 3 7
Affiliations

Affiliations

  • 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.
PMID: 38568078 DOI: 10.1111/jcmm.18201
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.

Keywords

Neuropilin 1; Semaphorin 3A; Wnt signalling; bone homeostasis; bone remodelling; dorsal root ganglion; mesenchymal stem cells; osteogenic differentiation; osteoporosis; peripheral nerve.

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