P101 Ameliorates TiO NP-Induced Bone Injury in Young Rats by Remodeling the Gut Microbiota and Inhibiting the Production of Pro-Inflammatory Cytokines.

PURPOSE

To evaluate the therapeutic effect of oral administration of P101 (P101) on skeletal injury in young rats exposed to titanium dioxide nanoparticles (TiO NPs), and explore the potential mechanism.

METHODS

Four-week-old male rats were orally administration to TiO NPs and supplemented with P101 2 hours later for 4 weeks. The growth and development, food intake, bone metabolism and serum inflammatory markers of the rats were evaluated. Their tibias were observed and evaluated using microcomputed tomography (micro-CT), tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry (IHC) and real-time quantitative PCR (RT-qPCR). We observed the tibia growth plate using safranin and fast green staining. 16S rDNA sequence analysis of fecal samples was performed to observe changes in the gut microbiota.

RESULTS

Our results showed that TiO NPs can lead to bone growth inhibition and osteoporosis, induce intestinal flora imbalance, and induce inflammation in young rats. Further mechanistic studies suggested that TiO NPs disrupts intestinal flora and increases serum IL-1β levels, which increased the expression of RANKL in bone, thereby enhancing osteoclast differentiation and function, leading to bone loss. Through a P101 supplementation experiment, we found that P101 ameliorated the inflammation and osteoporosis on bone caused by TiO NPs.

CONCLUSION

This study showed that the mechanism by which P101 alleviates bone damage caused by TiO NPs may be through restoring intestinal microbial homeostasis and inhibiting inflammatory response.