Advanced oxidation protein products accelerate bone deterioration in aged rats

• Published in: Experimental gerontology Vol. 50; pp. 64 - 71
• Main Authors: Zeng, Ji-Huan, Zhong, Zhao-Ming, Li, Xiao-Dan, Wu, Qian, Zheng, Shuai, Zhou, Jian, Ye, Wen-Bin, Xie, Fang, Wu, Xiu-Hua, Huang, Zhi-Ping, Chen, Jian-Ting
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.02.2014
• Subjects: Acetophenones - pharmacology; Advanced Oxidation Protein Products - antagonists & inhibitors; Advanced Oxidation Protein Products - blood; Advanced Oxidation Protein Products - toxicity; Aged rats; Aging - physiology; Animals; Antioxidants - pharmacology; AOPPs; Biomarkers - blood; Biomechanical Phenomena - drug effects; Bone Density - drug effects; Bone Density - physiology; Bone deterioration; Bone Remodeling - drug effects; Bone Remodeling - physiology; Enzyme Inhibitors - pharmacology; Femur - drug effects; Femur - physiopathology; Lumbar Vertebrae - drug effects; Lumbar Vertebrae - pathology; Lumbar Vertebrae - physiopathology; Male; NADPH Oxidases - antagonists & inhibitors; Osteoporosis - blood; Osteoporosis - chemically induced; Osteoporosis - physiopathology; Oxidative stress; Oxidative Stress - physiology; Rats; Rats, Sprague-Dawley; Senile osteoporosis; Tibia - drug effects; Tibia - pathology; Tibia - physiopathology; Oxidative stress; Aged rats; Senile osteoporosis; AOPPs; Bone deterioration
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2013.11.014

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 8weeks or 16weeks, 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. •AOPPs are important pathological factors in many diseases, such as diabetic kidney, atherosclerosis.•18-month-old male Sprague Dawley rats were used as age related bone loss model.•Effects of AOPPs on bone were investigated from bone turnover, t-BMD, microstructures and biochemical quality.•AOPPs greatly fluctuated bone turnover pattern, decreased t-BMD and promoted bone microstructural degeneration.•AOPPs-induced perturbations could be prevented by apocynin, which was a NADPH oxidase inhibitor.