Cell Culture Laboratory, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
J Cell Biochem. 2018 Nov;119(10):8441-8449. doi: 10.1002/jcb.27060. Epub 2018 Jun 22.
Among bone morphogenetic proteins (BMPs), BMP-9 has been described as one with higher osteogenic potential. Here, we aimed at evaluating the effect of BMP-9 on the osteoblast differentiation of cells grown on titanium (Ti) with nanotopography, a well-known osseoinductive surface. MC3T3-E1 cells were grown either in absence or presence of BMP-9 (20 nM) on Ti with nanotopography (Ti-Nano) or machined Ti (Ti-Machined) for up to 21 days to evaluate the gene expression of RUNX2, osterix, osteocalcin, bone sialoprotein, SMAD6 and SMAD4, protein expression of SMAD4, ALP activity and extracellular matrix mineralization. As expected BMP-9 increased osteoblast differentiation irrespective of Ti surface topography; however, the cells grown on Ti-Nano were more responsible to BMP-9 compared with cells grown on Ti-machined. This could be, at least in part, due to the fact that Ti-Nano may act on both ways, by increasing the activation (SMAD4) and decreasing the inhibition (SMAD6) of the signaling pathway triggered by BMP-9, while Ti-Machined only decrease the inhibition (SMAD6) of this pathway. In conclusion, the combination of the osteogenic potential of BMP-9 with the osseoinductive capacity of Ti-Nano could be a promising strategy to favor the osseointegration of Ti implants.
在骨形态发生蛋白（BMPs）中，BMP-9 被描述为具有更高成骨潜能的蛋白。在这里，我们旨在评估 BMP-9 对具有纳米形貌的钛（Ti）上细胞成骨分化的影响，这是一种众所周知的骨诱导表面。MC3T3-E1 细胞在不存在或存在 BMP-9（20 nM）的情况下分别在具有纳米形貌的 Ti（Ti-Nano）或机械加工 Ti（Ti-Machined）上培养长达 21 天，以评估 RUNX2、osterix、骨钙素、骨涎蛋白、SMAD6 和 SMAD4 的基因表达、SMAD4 的蛋白表达、碱性磷酸酶活性和细胞外基质矿化。不出所料，BMP-9 增加了成骨分化，而与 Ti 表面形貌无关；然而，与在 Ti 机械加工上生长的细胞相比，在 Ti-Nano 上生长的细胞对 BMP-9 的反应更敏感。这至少部分是因为 Ti-Nano 可能通过增加 BMP-9 触发的信号通路的激活（SMAD4）和减少抑制（SMAD6）来发挥作用，而 Ti-Machined 仅减少该通路的抑制（SMAD6）。总之，BMP-9 的成骨潜能与 Ti-Nano 的骨诱导能力相结合，可能是促进 Ti 植入物骨整合的一种有前途的策略。
