Oral Exposure to ZnO Nanoparticles Disrupt the Structure of Bone in Young Rats via the OPG/RANK/RANKL/IGF-1 Pathway

Xinyue Xu,1,* Yizhou Tang,2,* Yuanyuan Lang,3,* Yanling Liu,1 Wenshu Cheng,1 Hengyi Xu,2 Yang Liu1 1Department of Pediatrics, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 2State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, People’s Republic of China; 3Medical Imaging Center, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang LiuDepartment of Pediatrics, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang 330006 Jiangxi Province, People’s Republic of ChinaTel +86-791-8631-1209Email ocean3166@yeah.netHengyi XuState Key Laboratory of Food Science and Technology, Nanchang University, 235 Nanjing East Road, Nanchang 330047, People’s Republic of ChinaTel +86-791-8830-4447-ext-9520Fax +86-791-8830-4400Email kidyxu@163.comPurpose: To evaluate the effects of ZnO NPs on bone growth in rats and explore the possible mechanisms of action.Materials and Methods: Three-week-old male rats received ultrapure water or 68, 203, and 610 mg/kg zinc oxide nanoparticles (ZnO NPs) for 28 days, orally.Results: The high-dosage groups caused significant differences in weight growth rate, body length, and tibia length (P< 0.05), all decreasing with increased ZnO NP dosage. There were no significant differences in body mass index (BMI) (P> 0.05). The zinc concentration in liver and bone tissue increased significantly with increased ZnO NP dosage (P< 0.05). Clearly increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were observed in the 610 mg/kg ZnO NP group (P> 0.05), whereas alkaline phosphatase (ALP) increased in the 610 mg/kg ZnO NP group (P< 0.05). Significant differences in insulin-like growth factor type 1 (IGF-1) levels and a decrease in calcium (Ca) levels were observed in 203 and 610 mg/kg ZnO NP groups (P< 0.05). Phosphorus (P) levels increased and the Ca/P ratio decreased in the 610 mg/kg ZnO NP group (P< 0.05). Micro-computed tomography (micro-CT) of the tibia demonstrated signs of osteoporosis, such as decreased bone density, little trabecular bone structure and reduced cortical bone thickness. Micro-CT data further demonstrated significantly decreased bone mineral density (BMD), trabecular number (Tb.N), and relative bone volume (BV/TV) with increasing dosage of ZnO NPs. Osteoprotegerin (OPG) expression and the ratio of OPG to receptor activator of nuclear factor-κB ligand (RANKL) were statistically lower in the 610 mg/kg ZnO NP group (P< 0.05), whereas RANKL expression did not change significantly (P> 0.05).Conclusion: We infer that ZnO NPs affect bone growth in young rats directly or indirectly by altering IGF-1 levels. Overall, the results indicate that ZnO NPs promote osteoclast activity and increase bone loss through the OPG/RANK/RANKL/IGF-1 pathway.Keywords: ZnO NPs, young rats, bone growth, OPG/RANK/RANKL/IGF-1 pathway