Effect of reactive oxygen species overproduction on osteogenesis of porous titanium implant in the present of diabetes mellitus
Effect of reactive oxygen species overproduction on osteogenesis of porous titanium implant in the present of diabetes mellitus
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DOI：
10.1016/j.biomaterials.2012.12.023
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发表时间：
2013-03-01
期刊：
影响因子：
14
通讯作者：
Zhang, Zhi-Yong
中科院分区：
文献类型：
--
作者：
Feng, Ya-Fei;Wang, Lin;Zhang, Zhi-Yong
临床证据表明，糖尿病是钛种植体治疗的主要危险因素，失败率高，骨整合差，但涉及的潜在机制仍不清楚。我们推测，在糖尿病条件下，活性氧物种(ROS)的过度产生可能导致多孔钛植入物(PTI)的成骨功能受损。为了验证这一假设，我们将原代兔成骨细胞培养到PTI上，并研究了在正常血清(NS)、糖尿病血清(DS)、DS+NAC(有效的ROS抑制剂)和NS+H_2O_2(氧化剂)的作用下，PTI的体内性能。结果显示，糖尿病诱导细胞明显凋亡，成骨细胞功能下降，细胞附着和形态受损，细胞增殖和分化减少，体内成骨能力下降，而线粒体功能障碍导致细胞内ROS生成增加。NAC清除ROS可显著减轻PTI内细胞凋亡和成骨细胞功能障碍，促进骨内生长。此外，过氧化氢治疗对细胞行为的不利影响与糖尿病相似。这项研究进一步加深了我们对ROS过度产生在糖尿病引起的钛种植体成骨障碍中的潜在作用的认识，并表明抗氧化治疗是提高糖尿病患者PTI治疗效果的一种有前途的策略。(C)2012爱思唯尔有限公司。保留所有权利。
Clinical evidence indicates diabetes as a major risk factor for titanium implant treatment with high failure rates and poor osteointegration, but the underlying mechanism involved remains elusive. We hypothesize that reactive oxygen species (ROS) overproduction may contribute to the impaired osteogenesis of porous titanium implants (pTi) under diabetic conditions. To test this hypothesis, we cultured primary rabbit osteoblasts onto pTi and studied the cellular performance when subjected to normal serum (NS), diabetic serum (DS), DS + NAC (a potent ROS inhibitor) and NS + H2O2(an oxidant),In-vivo performance of pTi was investigated by transplanting them intofemoral condyledefects of diabetic rabbits, which received vehicle or NAC treatment respectively. Results showed that diabetic conditions induced significant cellular apoptosis, depressed osteoblast function evidenced by impaired cell attachment and morphology, decreased cell proliferation and differentiation, and compromised in-vivo osteogenesis of pTi, while cellular ROS generation was increased derived from mitochondrial dysfunction. Scavenging ROS with NAC markedly attenuated cell apoptosis and osteoblast dysfunction, and improved bone ingrowth within pTi. Furthermore, treatment with H2O2 exerted similar adverse effect on cellular behavior as diabetes. This study furthers our knowledge on the potential role of ROS overproduction in the diabetes-induced impaired osteogenesis of titanium implants, and indicates anti-oxidative treatment as a promising strategy to promote the treatment efficacy of pTi in diabetic patients. (C) 2012 Elsevier Ltd. All rights reserved.