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Stem Cells International
Volume 2016, Article ID 2545214, 13 pages
Research Article

Semaphorin 3A Shifts Adipose Mesenchymal Stem Cells towards Osteogenic Phenotype and Promotes Bone Regeneration In Vivo

1State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Implant Dentistry, School of Stomatology, Fourth Military Medical University, Xi’an 710032, China
2Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
3Department of Plastic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
4Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, China

Received 18 June 2016; Revised 17 August 2016; Accepted 18 August 2016

Academic Editor: Giacomina Brunetti

Copyright © 2016 Xiangwei Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Adipose mesenchymal stem cells (ASCs) are considered as the promising seed cells for bone regeneration. However, the lower osteogenic differentiation capacity limits its therapeutic efficacy. Identification of the key molecules governing the differences between ASCs and BMSCs would shed light on manipulation of ASCs towards osteogenic phenotype. In this study, we screened semaphorin family members in ASCs and BMSCs and identified Sema3A as an osteogenic semaphorin that was significantly and predominantly expressed in BMSCs. The analyses in vitro showed that the overexpression of Sema3A in ASCs significantly enhanced the expression of bone-related genes and extracellular matrix calcium deposition, while decreasing the expression of adipose-related genes and thus lipid droplet formation, resembling a BMSCs phenotype. Furthermore, Sema3A modified ASCs were then engrafted into poly(lactic-co-glycolic acid) (PLGA) scaffolds to repair the critical-sized calvarial defects in rat model. As expected, Sema3A modified ASCs encapsulation significantly promoted new bone formation with higher bone volume fraction and bone mineral density. Additionally, Sema3A was found to simultaneously increase multiple Wnt related genes and thus activating Wnt pathway. Taken together, our study here identifies Sema3A as a critical gene for osteogenic phenotype and reveals that Sema3A-modified ASCs would serve as a promising candidate for bettering bone defect repair.