The healing of alveolar bone defects with novel bio-implants composed of Ad-BMP9-transfected rDFCs and CHA scaffolds

Li Nie,Ting Cai,Xia Yang,Wenping Luo,Conghua Li,Liang Duan,Xingqi Zeng,Zhou Pengfei,Ye Qiu,Enyi Huang,Yan Zhang

doi:10.1038/s41598-017-06548-7

Abstract

Cells, scaffolds, and growth factors play important roles in bone regeneration. Bone morphogenetic protein 9 (BMP9), a member of BMP family, could facilitate osteogenesis by regulating growth factors and promoting angiogenesis. Similar to other stem cells, rat dental follicle stem cells (rDFCs), the precursor cells of cementoblasts, osteoblasts and periodontal ligament cells, can self-renew and exhibit multipotential capacity. Coralline hydroxyapatite (CHA) has good biocompatibility and conductivity required for bone tissue engineering. Here, we reported that BMP9 could enhance the osteogenic differentiation of rDFCs in cell culture. Moreover, our results suggested that BMP9 acted through the Smad1/5/8 signaling pathway. We also produced a novel scaffold that encompasses bio-degradable CHA seeded with recombinant adenoviruses expressing BMP9-transfected rDFCs (Ad-BMP9-transfected rDFCs). With this implant, we achieved more alveolar bone regeneration in the alveolar bone defect compared to blank group, CHA group and rDFCs group. Our results provided a novel bio-implants composed of Ad-BMP9-transfected rDFCs and CHA scaffolds and its mechanism is regarding the activation of Smad1/5/8 signaling pathway in BMP9-induced rDFCs osteogenesis.

Highlights

Periodontitis is one of the most common oral diseases[1]
We have demonstrated that Bone morphogenetic protein 9 (BMP9) could effectively promote the osteogenic differentiation of rat dental follicle stem cells (rDFCs) by regulating P38 and ERK1/2 MAPK manner, a Smad-independent signaling pathway[11]
We demonstrated that rDFCs could thrive on the Coralline hydroxyapatite (CHA) scaffold and BMP9 could strongly promote the osteogenesis of rDFCs

Summary

Introduction

Periodontitis is one of the most common oral diseases[1]. It has been characterized as a chronic infectious and inflammatory disease, which affects periodontal tissues and eventually leads to tooth loss[2]. Our previous study demonstrated that BMP9 could stimulate the expression of osteogenic differentiation genes in rDFCs. further animal studies are intensely necessary to further characterize the osteogenetic potential of BMP9-induced cells in vivo. Recombinant human bone morphogenetic protein 9 (rhBMP9) exhibited significantly weaker osteogenic activity, compared with that induced by recombinant adenoviruses expressing BMP9 (Ad-BMP9)[19]. For these reasons, we considered investigating the possibility of seeding BMP9-induced rDFCs on scaffolds to repair periodontal alveolar bone defect in vivo. We have demonstrated that BMP9 could effectively promote the osteogenic differentiation of rDFCs by regulating P38 and ERK1/2 MAPK manner, a Smad-independent signaling pathway[11]. It still remains unclear whether BMP9 could induce the osteogenic differentiation in rDFCs by activating the Smad-dependent signaling pathway directly or indirectly

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Conclusion