Yao Shaomian, He Hongzhi, Gutierrez Dina L, Rad Maryam Rezai, Liu Dawen, Li Chunhong, Flanagan Michael, Wise Gary E
Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, La., USA.
Cells Tissues Organs. 2013;198(6):438-47. doi: 10.1159/000360275. Epub 2014 Apr 8.
The dental follicle (DF) plays an essential role in tooth eruption via regulation of bone resorption and bone formation. Bone morphogenetic protein-6 (BMP6) expression in the DF is coincident with bone growth in the tooth crypt. DF stem cells (DFSCs) have been shown to possess strong osteogenic capability. This study aims to determine the expression of BMP6 in DFSCs and to elucidate the role of BMP6 in the osteogenesis of DFSCs. DFSCs and their non-stem cell counterpart, DF cells (DFCs), were obtained from the DFs of rat pups. We showed that expression of BMP6 was significantly higher in the DFSCs than in the DFCs. DFSCs lost osteogenic capability during in vitro expansion, and DFSCs in late passages had reduced BMP6 expression as compared to early passages of DFSCs when they were subjected to osteogenic induction. Addition of exogenous human recombinant BMP6 (hrBMP6) to the osteogenic medium dramatically enhanced the osteogenesis of the late-passage DFSCs. Knockdown of BMP6 by short interfering RNA in the DFSCs in early passages resulted in a decrease in osteogenesis, which could be restored by addition of hrBMP6. We concluded that DFSCs need to express high levels of BMP6 to maintain their osteogenesis capability. Increased BMP6 expression seen in vivo in the DF may reflect the activation of DFSCs for osteogenic differentiation for bone growth during tooth eruption.
牙囊(DF)通过调节骨吸收和骨形成在牙齿萌出过程中发挥着重要作用。牙囊中骨形态发生蛋白6(BMP6)的表达与牙胚中的骨生长同步。牙囊干细胞(DFSCs)已被证明具有强大的成骨能力。本研究旨在确定BMP6在DFSCs中的表达,并阐明BMP6在DFSCs成骨过程中的作用。从新生大鼠的牙囊中获取DFSCs及其非干细胞对应物,即牙囊细胞(DFCs)。我们发现,DFSCs中BMP6的表达明显高于DFCs。DFSCs在体外扩增过程中丧失了成骨能力,与早期传代的DFSCs相比,晚期传代的DFSCs在接受成骨诱导时BMP6表达降低。向成骨培养基中添加外源性人重组BMP6(hrBMP6)可显著增强晚期传代DFSCs的成骨能力。早期传代的DFSCs中通过短发夹RNA敲低BMP6导致成骨减少,添加hrBMP6可恢复成骨。我们得出结论,DFSCs需要表达高水平的BMP6以维持其成骨能力。在牙囊体内观察到的BMP6表达增加可能反映了在牙齿萌出过程中,DFSCs被激活以进行成骨分化促进骨生长。