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首页> 外文期刊>Journal of biomedical materials research, Part A >The roles of PI3K/Akt signaling pathway in regulating MC3T3-E1 preosteoblast proliferation and differentiation on SLA and SLActive titanium surfaces.
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The roles of PI3K/Akt signaling pathway in regulating MC3T3-E1 preosteoblast proliferation and differentiation on SLA and SLActive titanium surfaces.

机译：PI3K / Akt信号通路在调节SLA和SLActive钛表面上MC3T3-E1成骨细胞增殖和分化中的作用。

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Chemical modification to produce a hydrophilic microrough titanium (Ti) implant surface has been shown to increase osseointegration compared with microrough topography alone. This study aimed to investigate the roles of PI3K/Akt signaling pathway in regulating proliferation and differentiation of osteoblasts in response to surface microroughness and hydrophilicity. Ti disks were manufactured to present different surface morphologies: a smooth pretreatment surface (PT), a rough hydrophobic surface that was sand-blasted, large-grit, acid-etched (SLA), and an SLA surface with the same roughness that was chemically modified to possess high wettability/hydrophilicity (SLActive/modSLA). MC3T3-E1 cells were cultured on these substrates with or without LY294002, a PI3K inhibitor, and their behaviors, including cell viability (MTT colorimetric assay), alkaline phosphatase (ALP) activity, and osteogenic genes expression of osteopontin (OPN) and osteocalcin (OCN) were measured. Western blot was applied to detect the expression of PI3K/Akt signal pathway proteins. The results showed that a decrease in osteoblast proliferation associated with the Ti surfaces (SLActive > SLA > PT) correlated with an increase in activity of the osteogenic differentiation markers ALP. The peak of ALP activity appeared earlier at 7 days for the SLActive surfaces compared with the SLA and PT surfaces. Osteoblast proliferation, as well as the level of p-Akt, was significantly inhibited by LY294002 in all three Ti surfaces. The top value of ALP activity was increased with the inhibition of PI3K/Akt signaling pathway while the time of the peak appeared was not advanced. The expression levels of OPN and OCN were upregulated by the effect of surface roughness and hydrophilicity, which were further enhanced by LY294002. In conclusion, osteogenic responses to SLActive surface were moderately better than the SLA surface and protein expression studies indicated that PI3K/Akt signaling activation may be responsible for this increased osteogenic differentiation. Surface microroughness and hydrophilicity may affect osteoblast functions by targeting osteoblast proliferation and the early stage of osteoblast differentiation through PI3K/Akt signaling pathway.
机译：与单独的微粗糙形貌相比，化学修饰以产生亲水性的微粗糙钛（Ti）植入物表面已显示出增加的骨整合。这项研究旨在调查PI3K / Akt信号通路在调节成骨细胞响应表面微粗糙度和亲水性的增殖和分化中的作用。生产的Ti圆盘具有不同的表面形态：光滑的预处理表面（PT），喷砂处理的粗糙疏水表面，粗砂，酸蚀（SLA）以及化学粗糙度相同的SLA表面改性后具有高润湿性/亲水性（SLActive / modSLA）。在有或没有LY294002，PI3K抑制剂的情况下，在这些底物上培养MC3T3-E1细胞，并研究其行为，包括细胞活力（MTT比色测定），碱性磷酸酶（ALP）活性以及骨桥蛋白（OPN）和骨钙素的成骨基因表达（ OCN）。免疫印迹用于检测PI3K / Akt信号通路蛋白的表达。结果表明，与Ti表面相关的成骨细胞增殖减少（SLActive> SLA> PT）与成骨分化标记ALP活性增加有关。与SLA和PT表面相比，SLActive表面的ALP活性峰值出现在7天之前。 LY294002在所有三个Ti表面中均显着抑制成骨细胞的增殖以及p-Akt的水平。 ALP活性的最高值随PI3K / Akt信号通路的抑制而增加，而出现峰的时间并未提前。 OPN和OCN的表达水平受表面粗糙度和亲水性的影响而被上调，而LY294002进一步增强了OPN和OCN的表达。总之，对SLActive表面的成骨反应比SLA表面要好一些，蛋白质表达研究表明PI3K / Akt信号激活可能是这种成骨分化增加的原因。表面微粗糙度和亲水性可能通过靶向成骨细胞增殖和通过PI3K / Akt信号通路的成骨细胞分化早期而影响成骨细胞功能。

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