Anatase and Rutile TiO2 Nanoparticles Lead Effective Bone Damage in Young Rat Model via the IGF-1 Signaling Pathway

Wenshu Cheng,1,* Xinyue Xu,1,* Yuanyuan Lang,2,* Zugen Cheng,1 Mohammad Rizwan,1 Xiaomin Tang,1 Lixin Xie,1 Yanling Liu,1 Hengyi Xu,3 Yang Liu1 1Department of Pediatrics, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, People’s Republic of China; 2Medical Imaging Center, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, People’s Republic of China; 3State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi Province, 330047, 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, Jiangxi Province, People’s Republic of ChinaTel +0086-791-8631-1209Email ocean3166@yeah.netPurpose: To evaluate the effects of anatase and rutile TiO2 nanoparticles (NPs) on the growth and development of bones in young rats and explore their possible mechanisms.Methods: Three-week-old male rats were orally administered anatase TiO2 NPs and rutile TiO2 NPs for 28 days. The indicators of rat growth and development, liver function, bone metabolism, and insulin-like growth factor-1 (IGF-1) levels were evaluated. Micro-computed tomography (micro-CT) and immunohistochemistry were used to evaluate the tibia.Results: No significant differences were observed among growth and development indicators in young rats. Significant differences were found in IGF-1 levels, phosphorus levels, and liver function. Micro-CT revealed osteoporosis in the bones. The micro-CT data supported the same result. Bone immunohistochemistry results showed that the expression of osteoprotegerin (OPG) was decreased and the expression of receptor activator of nuclear factor-κB ligand (RANKL) and cathepsin K (CTSK) was increased.Conclusion: This study demonstrated that TiO2 NPs can damage bones via the IGF-1/OPG/RANKL/CTSK pathway in young rats. Furthermore, rutile TiO2 NPs damaged the bones more seriously than anatase TiO2 NPs.Keywords: TiO2 NPs, different crystal forms, IGF-1/OPG/RANKL/CTSK pathway, young rats, bone growth