表面粗糙度调节的反应MG63 osteoblast-like细胞1,25 - D (OH)(2)(3)通过磷脂酶(2)活动的监管和激活的蛋白激酶。

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罗曼CH, Sagun R小,西尔维娅六世,科克伦DL, Dean DD Boyan BD,施瓦茨Z

表面粗糙度调节的反应MG63 osteoblast-like细胞1,25 - D (OH)(2)(3)通过磷脂酶(2)活动的监管和激活的蛋白激酶。

d生物医学研究》1999年11月,47 (2):139 - 51。

PubMed ID
10449625 (在PubMed
]
文摘

植入物表面粗糙度影响成骨细胞增殖、分化和当地的生产因素。此外,成骨细胞的响应性系统性激素如1、25 - D (OH)(2)(3)改变了表面粗糙度的影响;养钛表面粗糙度的影响,25 - D (OH)(2)(3)协同。前列腺素E(2)(铂族元素(2)似乎是参与调节细胞表面粗糙度的影响,以及应对1,25 - D (OH) (2) (3)。然而,目前尚不清楚,通过信号通路表面粗糙度对其影响成骨细胞的反应,25 - (OH) (2) (3)。目前的研究调查了潜在作用的蛋白激酶A (PKA),磷脂酶A(2)(人民解放军(2))和蛋白激酶C (PKC)在这个过程中。MG63 osteoblast-like人类骨肉瘤细胞培养在cpTi磁盘使用R (a)值为0。54 microm (PT), 4.14 microm (SLA),或4.92 microm (TPS)。PKA抑制是通过添加H8文化;同样,解放军(2)与阿的平抑制或激活蜂毒肽,与白屈菜赤碱和PKC抑制。 Inhibitors or activators were included in the culture media through the entire culture period or for the last 24 h of culture. In addition, cultures were treated for 24 h with inhibitors or activators in the presence of 1,25-(OH)(2)D(3). The effects on cell number and alkaline phosphatase specific activity were determined after 24 h; PKC activity was determined after 9 min and at 24 h. Cell number was reduced on rough surfaces, and alkaline phosphatase activity was increased. 1,25-(OH)(2)D(3) had a synergistic effect with surface roughness on alkaline phosphatase. However, neither surface roughness nor 1,25-(OH)(2)D(3) had an effect on PKC. H8 treatment for 24 h inhibited cell number and alkaline phosphatase on all surfaces; however, when it was present throughout the culture period, the PKA inhibitor had no effect on cell number, but decreased alkaline phosphatase-specific activity. H8 reduced the 1,25-(OH)(2)D(3)-mediated effect on cell number and alkaline phosphatase. Quinacrine inhibited cell proliferation and alkaline phosphatase on all surfaces and further reduced the 1,25-(OH)(2)D(3)-dependent decreases in both parameters. Melittin had no effect when applied for 24 h and did not modify the 1,25-(OH)(2)D(3) effect; however, when present throughout the culture period, it caused a decrease in proliferation and an increase in enzyme activity. Chelerythrine, the PKC inhibitor, only inhibited cell proliferation when it was present throughout the entire culture period. However, it decreased alkaline phosphatase in cultures treated for 24 h, but increased enzyme activity when it was present for the entire culture period. The results indicate that surface roughness and 1,25-(OH)(2)D(3) both mediate their effects through PLA(2) which catalyzes the rate-limiting step in PGE(2) production. Further downstream, PGE(2) activates PKA. Surface roughness-dependent effects are also mediated through PKC, but only after the cells have reached confluence and are undergoing phenotypic maturation. The effect of surface roughness on responsiveness to 1,25-(OH)(2)D(3) is mediated through PLA(2)/PKA and not through PKC.

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药物靶点
药物 目标 生物 药理作用 行动
阿的平 85/88 kDa calcium-independent磷脂酶A2 蛋白质 人类
是的
抑制剂
细节