Griffith University, Southport, Queensland, Australia.
Clin Oral Implants Res. 2011 Apr;22(4):373-81. doi: 10.1111/j.1600-0501.2010.02112.x.
To determine the temporal gene expression profile associated with the early healing events during osseointegration in a human model.
Nine solid screw-type cylindrical titanium implants, 4 mm long and 2.8 mm wide, with a chemically modified surface (SLActive) were surgically inserted in the retromolar area of nine human volunteers. The devices were removed using a trephine following 4, 7 and 14 days of healing. The tissue surrounding the implant was harvested, total RNA was extracted and microarray analysis was carried out to identify the differences in the transcriptome between days 4, 7 and 14.
Gene ontology (GO) analysis of the temporal transcriptional changes was characteristic of a maturing, osteogenic process over the course of the study (4-14 days). At day 4, a gene expression profile associated with proliferation and immuno-inflammatory processes was predominant. However, by day 14, by far the most predominant mechanisms were associated with skeletogenesis, with the GO categories of skeletal system development, bone development and ossification being predominant, with the majority of changes occurring between days 7 and 14. Furthermore, the biological processes of angiogenesis and neurogenesis were also predominant by day 14. In terms of signal transduction, I-κB kinase/NF-κB cascade was predominant at day 4, whereas TGF-β/BMP, Wnt and Notch signalling were all associated with the osteogenic process over the duration of the study. Furthermore, Ras and Rho protein signal transduction was regulated throughout the osseointegration process.
The temporal transcriptional changes during osseointegration involve the expression of proliferation and immuno-inflammatory response associated genes during the early stages of osseointegration, which are ultimately replaced by genes associated with the biological processes of skeletogenesis, angiogenesis and neurogenesis. The early immuno-inflammatory changes appear to be regulated via the I-κB kinase/NF-κB cascade, whereas the later osteogenesis-related mechanisms are regulated by TGF-β/BMP, Notch and Wnt signaling.
确定与人类模型中骨整合早期愈合事件相关的时间基因表达谱。
将 9 个长 4 毫米、宽 2.8 毫米、具有化学改性表面（SLActive）的实心螺钉型圆柱形钛植入物外科植入 9 名志愿者的磨牙后区。在愈合后 4、7 和 14 天，使用环钻取出装置。从植入物周围采集组织，提取总 RNA，并进行微阵列分析以鉴定不同天数（4、7 和 14 天）之间转录组的差异。
对时间转录变化的基因本体论（GO）分析表明，在整个研究过程（4-14 天）中，存在一个成熟的成骨过程。在第 4 天，与增殖和免疫炎症过程相关的基因表达谱占主导地位。然而，到第 14 天，迄今为止最主要的机制与骨骼发生有关，GO 类别包括骨骼系统发育、骨发育和骨化占主导地位，大多数变化发生在第 7 天和第 14 天之间。此外，血管生成和神经发生的生物学过程在第 14 天也占主导地位。就信号转导而言，I-κB 激酶/NF-κB 级联在第 4 天占主导地位，而 TGF-β/BMP、Wnt 和 Notch 信号都与整个骨整合过程中的成骨过程有关。此外，Ras 和 Rho 蛋白信号转导在整个骨整合过程中受到调节。
骨整合过程中的时间转录变化涉及增殖和免疫炎症反应相关基因在骨整合早期的表达，这些基因最终被与骨骼发生、血管生成和神经发生的生物学过程相关的基因所取代。早期的免疫炎症变化似乎通过 I-κB 激酶/NF-κB 级联调节，而后期与成骨相关的机制则由 TGF-β/BMP、Notch 和 Wnt 信号调节。
