Chen Fuguo, Bi Dan, Cao Guangqing, Cheng Chen, Ma Sunxiang, Liu Yang, Cheng Kaixiang
a Department of Plastic and Reconstructive Surgery , Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China.
Connect Tissue Res. 2018 May;59(3):223-232. doi: 10.1080/03008207.2017.1353085. Epub 2017 Jul 31.
Human dermal-derived fibroblast cells (hDDFCs) are multipotent. Bone morphogenetic proteins (BMPs) are a group of cytokines that promote different developmental processes, including the formation of bone. BMPs can promote hDDFC osteogenesis, but the role of BMP7 in hDDFC osteogenesis in vitro and bone formation in vivo has not been investigated in depth.
hDDFCs were stably transfected with a human BMP7 recombinant adenovirus and osteogenic differentiation was examined by alkaline phosphatase staining and calcium accumulation. In addition, we measured the expression of osteoblast-related genes. To examine osteogenesis in vivo, we injected C57BL/6 nude mice with adenovirus-transfected hDDFCs in a calcium alginate hydrogel and examined bone formation using soft X-ray, histological, and immunohistochemical analyses.
Our findings showed that adenovirus-mediated BMP7 expression promoted osteogenic differentiation of hDDFCs and enhanced expression of osteoblast-related genes in vitro. Cells infected with BMP7 adenoviruses showed enhanced bone formation and osteoblast-related gene expression in vivo after the injection of hDDFC-hydrogel mixture.
Taken together, our data indicate that BMP7 significantly promotes hDDFC osteogenesis, and confirm that infecting hDDFCs with BMP7-expressing adenoviruses is a useful tool for bone tissue engineering.
人真皮来源的成纤维细胞(hDDFCs)具有多能性。骨形态发生蛋白(BMPs)是一组促进不同发育过程(包括骨形成)的细胞因子。BMPs可促进hDDFC的成骨作用,但BMP7在体外hDDFC成骨作用及体内骨形成中的作用尚未得到深入研究。
用人类BMP7重组腺病毒稳定转染hDDFCs,并通过碱性磷酸酶染色和钙积累检测成骨分化。此外,我们检测了成骨细胞相关基因的表达。为了在体内检测成骨情况,我们将腺病毒转染的hDDFCs注射到C57BL/6裸鼠的海藻酸钙水凝胶中,并通过软X射线、组织学和免疫组织化学分析检测骨形成。
我们的研究结果表明,腺病毒介导的BMP7表达促进了hDDFCs的成骨分化,并增强了体外成骨细胞相关基因的表达。注射hDDFC-水凝胶混合物后,感染BMP7腺病毒的细胞在体内显示出增强的骨形成和成骨细胞相关基因表达。
综上所述,我们的数据表明BMP7显著促进hDDFC的成骨作用,并证实用表达BMP7的腺病毒感染hDDFCs是骨组织工程的一种有用工具。