| Objective To investigate the mechanism of inhibiting titanium partical-induced osteolysis around the skull with arctiin (ARC) in mice based on the changes of inflammatory factors and gut microbiota. Methods Twenty 7-week-old C57BL/6J female mice were randomly and evenly assigned to the following groups: blank group (SHAM), model group (Vehicle), ARC low-dose group, (L-ARC) and ARC high-dose group (H-ARC). During the following 14 days, mice in the experimental group were injected intraperitoneally with two different concentrations of ARC [5 and 10 mg/(kg·d)], respectively. Mice in the sham group and vehicle group were injected with 0.9 % NaCl every day. The following parameters of skulls, BMD, BV/TV, Tb.N, BS/BV, Tb.Sp, and Tb.Th were detected with micro-CT. The levels of TRACP5b, CTX, OCN, IL-6, TNF-α, and IL-10 in serum were detected with ELISA. 16S rRNA sequencing was used to analyze the structure and abundance of gut microbiota. Results BMD, BV/TV, Tb.N, BS/BV, Tb.Th, OCN, and IL-10 decreased significantly in Vehicle group compared to those in SHAM group (P<0.01, P<0.05). Tb.Sp, TRACP5b, CTX, IL-6, and TNF-α significantly increased (P<0.05, P<0.01). Compared to those in Vehicle group, BMD, BV/TV, Tb.N, BS/BV, Tb.Th, and OCN in L-ARC group had an increasing trend (P>0.05), Tb.Sp, TRACP5b, and CTX had a decreasing trend (P<0.05), TNF-α and IL-6 significantly decreased (P<0.05), and IL-10 significantly increased (P<0.05). Compared to those in Vehicle group, the levels of BMD, BV/TV, Tb.N, and IL-10 in H-ARC group significantly increased (P<0.05, P<0.01), the levels of TRACP5b, CTX, IL-6, and TNF-α significantly decreased (P<0.05, P<0.01), while the levels of BS/BV, Tb.Th, and OCN had an increasing trend (P>0.05), and Tb.Sp had a decreasing trend (P>0.05). At the phylum level, compared to that in SHAM group, firmicutes/bacteroidota (F/B) ratio had an increasing trend in Vehicle group (P>0.05). However, compared to that in Vehicle group, the F/B ratio in L-ARC and H-ARC groups significantly decreased (P<0.01). At the genus level, compared to that in SHAM group, the abundance of ileibacterium in Vehicle group had an increasing trend (P>0.05), the abundance of prevotellaceae_UCG-001 and rikenellaceae_RC9 in gut in Vehicle group had a decreasing trend (P>0.05). While compared to that in Vehicle group, the abundance of ileibacterium in ARC groups significantly decreased (P<0.05), the abundance of prevotellaceae UCG-001 and rikenellaceae RC9 in gut in ARC groups significantly increased (P<0.05). Conclusion ARC inhibits titanium partical-induced osteolysis in mice by suppressing inflammation and modulating the structure of gut microbiota in a dose-dependent manner. |