title: Effect of reactive oxygen species overproduction on osteogenesis of porous titanium implant in the present of diabetes mellitus.
abstract: Clinical evidence indicates diabetes as a majorrisk factor for titaniumimplant 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 culturedprimary 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 + H(2)O(2)(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, depressedosteoblast function evidenced by impairedcell attachment and morphology, decreased cell proliferation anddifferentiation, andcompromised in-vivo osteogenesis ofpTi, while cellular ROSgeneration 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 withH(2)O(2) 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.
authors.affiliation: Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ya-Fei
authors.initials: YF
authors.lastname: Feng
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.forename: Zhen-Sheng
authors.initials: ZS
authors.lastname: Ma
authors.forename: Ji-Wei
authors.initials: JW
authors.lastname: Zou
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Zhang
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D003920:Diabetes Mellitus / Q000503:physiopathology*; D006861:Hydrogen Peroxide / Q000032:analysis; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D018384:Oxidative Stress; D016062:Porosity; D019736:Prostheses and Implants; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014025:Titanium / Q000627:therapeutic use*
chemical_list: D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D006861:Hydrogen Peroxide; D014025:Titanium; D000469:Alkaline Phosphatase; D053148:Caspase 3