Anatase and Rutile TiO(2) Nanoparticles Lead Effective Bone Damage in Young Rat Model via the IGF-1 Signaling Pathway

PURPOSE: To evaluate the effects of anatase and rutile TiO(2) 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 TiO(2) NPs and rutile TiO(2) 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 TiO(2) NPs can damage bones via the IGF-1/OPG/RANKL/CTSK pathway in young rats. Furthermore, rutile TiO(2) NPs damaged the bones more seriously than anatase TiO(2) NPs.