Advanced oxidation protein products accelerate bone deterioration in aged rats.
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.
['Zeng|Ji-Huan|JH|', 'Zhong|Zhao-Ming|ZM|', 'Li|Xiao-Dan|XD|', 'Wu|Qian|Q|', 'Zheng|Shuai|S|', 'Zhou|Jian|J|', 'Ye|Wen-Bin|WB|', 'Xie|Fang|F|', 'Wu|Xiu-Hua|XH|', 'Huang|Zhi-Ping|ZP|', 'Chen|Jian-Ting|JT|']
D000098:Acetophenones D062107:Advanced Oxidation Protein Products D000375:Aging D000818:Animals D000975:Antioxidants D015415:Biomarkers D001696:Biomechanical Phenomena D015519:Bone Density D016723:Bone Remodeling D004791:Enzyme Inhibitors D005269:Femur D008159:Lumbar Vertebrae D008297:Male D019255:NADPH Oxidases D010024:Osteoporosis D018384:Oxidative Stress D051381:Rats D017207:Rats, Sprague-Dawley D013977:Tibia
Bone deterioration Aged rats AOPPs Senile osteoporosis Oxidative stress