title: Advanced oxidation protein products accelerate bone deterioration in aged rats.
abstract: Advanced oxidation protein products (AOPPs) are novel markers of oxidation-mediated protein damage, and accumulation of AOPPs is involved in many pathophysiological conditions. Our previous studies demonstrated that the serum level of AOPPs negatively correlated with the age-related change in bone mineral density (BMD) in rats and that AOPPs inhibited rat osteoblast-like cell proliferation and differentiation in vitro. However, whether AOPPs are involved in senile osteoporosis is still largely unknown. The present study aimed to test the hypothesis that accumulation of AOPPs might accelerate bone deterioration in aged rats. Seventy 18-month-old male Sprague Dawley (SD) rats were randomized to intravenous injection of vehicle, native rat serum albumin (RSA), AOPPs-modified RSA (AOPPs-RSA) with or without oral administration of apocynin (a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor), or apocynin alone. After treatment for 8 weeks or 16 weeks, seven rats in each group were sacrificed. Bone and blood samples were harvested for BMD measurement, micro-computed tomographic (micro-CT) imaging, and biochemical analysis of circulating bone biomarkers. Compared to RSA- or vehicle-treated rats, AOPPs-RSA-treated animals displayed significantly decreased total vertebral BMD and deteriorated microstructure in both the tibias and the lumbar vertebral bodies, which were associated with down-regulated plasma bone-specific alkaline phosphatase concentration and up-regulated tartrate-resistant acid phosphatase 5b concentration. These AOPPs-induced perturbations in aged rats could be prevented by the oral administration of apocynin. However, no significant differences in BMD were detected in the femurs or the biomechanical parameters tested between the different treatment groups. These data suggest that accumulation of AOPPs accelerates bone deterioration in aged rats, likely via the activation of NADPH oxidase. This study provides new information toward understanding the pathogenic basis of senile osteoporosis and may provide targets for intervention.
authors: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, China.
authors: Ji-Huan
authors: JH
authors: Zeng
authors: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, China. Electronic address: zhongzm@smu.edu.cn.
authors: Zhao-Ming
authors: ZM
authors: Zhong
authors: Department of Nursing, Guangdong General Hospital, China.
authors: Xiao-Dan
authors: XD
authors: Li
authors: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, China.
authors: Qian
authors: Q
authors: Wu
authors: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, China.
authors: Shuai
authors: S
authors: Zheng
authors: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, China.
authors: Jian
authors: J
authors: Zhou
authors: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, China.
authors: Wen-Bin
authors: WB
authors: Ye
authors: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, China.
authors: Fang
authors: F
authors: Xie
authors: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, China.
authors: Xiu-Hua
authors: XH
authors: Wu
authors: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, China.
authors: Zhi-Ping
authors: ZP
authors: Huang
authors: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, China. Electronic address: chenjt99@tom.com.
authors: Jian-Ting
authors: JT
authors: Chen
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D062107:Advanced Oxidation Protein Products / Q000037:antagonists & inhibitors / Q000097:blood / Q000633:toxicity*; D000375:Aging / Q000502:physiology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D001696:Biomechanical Phenomena / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005269:Femur / Q000187:drug effects / Q000503:physiopathology; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D010024:Osteoporosis / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
chemical_list: D000098:Acetophenones; D062107:Advanced Oxidation Protein Products; D000975:Antioxidants; D015415:Biomarkers; D004791:Enzyme Inhibitors; C056165:acetovanillone; D019255:NADPH Oxidases
keywords: AOPPs; Aged rats; Bone deterioration; Oxidative stress; Senile osteoporosis