期刊
BIOMATERIALS
卷 35, 期 9, 页码 2720-2729出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.12.029
关键词
Dentin regeneration; Nephroblastoma overexpressed (NOV, or CCN3); Dental pulp stem cell (DPSCs); Notch; Bone morphogenetic protein (BMP); Poly lactic-co-glycolic acid (PLGA) scaffold
资金
- Nature Science Foundation of China [81170934]
Dentin regeneration remains a great challenge in clinic. Dental pulp stem cells (DPSCs) actively contribute to dentinogenesis, which is orchestrated by a spectrum of signaling factors. However, the exact mechanism underlying the reparative dentin regeneration process is largely unknown and the application of DPSCs in the repair of dentin defect is thus limited. Here, using a rat reparative dentin regeneration model, we observed that DPSCs underwent a proliferation phase followed by a differentiation phase after dental injury. A transient elevation of nephroblastoma overexpressed (NOV, or CCN3) expression correlated with this progressive dental tissue restoration process. Further studies revealed that over-expression of CCN3 promoted human DPSCs proliferation via activation of Notch. Moreover, using cocultured cells (DPSCs/CCN3 and DPSCs) in vitro and the cocultured cells-poly (lactic-co-glycolic acid) (PLGA) scaffold complex in vivo, we demonstrated that CCN3 was capable of promoting mineralization in a non-cell autonomous manner through promoting secretion of BMP2. CCN3 can promote dentinogenesis by coordinating proliferation and odontoblastic differentiation of DPSCs via modulating Notch and BMP2 signaling pathways and CCN3 is a promising therapeutic target in dentin tissue engineering. (C) 2013 Elsevier Ltd. All rights reserved.
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