The
disruption of host–microbe homeostasis and uncontrolled
inflammatory response have been considered as vital causes for developing
periodontitis, subsequently leading to an imbalance between the bone
and immune system and the collapse of bone homeostasis. Consequently,
strategies to modulate the immune response and bone metabolization
have become a promising approach to prevent and treat periodontitis.
In this study, we investigated the cooperative effects of Nel-like
molecule type 1 (Nell-1) and gold nanoparticles (AuNPs) on macrophage
polarization, osteoclast differentiation, and the corresponding functions
in an experimental model of periodontitis in rats. Nell-1-combined
AuNPs in in vitro studies were found to reduce the
production of inflammatory factors (TNF-α, p < 0.0001; IL-6, p = 0.0012), modulate the ratio
of M2/M1 macrophages by inducing macrophage polarization into the
M2 phenotype, and inhibit cell fusion, maturation, and activity of
osteoclasts. Furthermore, the local application of Nell-1-combined
AuNPs in in vivo studies resulted in alleviation
of damages to the periodontal and bone tissues, modulation of macrophage
polarization and the activity of osteoclasts, and alteration of the
periodontal microbiota, in which the relative abundance of the probiotic Bifidobacterium increased (p < 0.05).
These findings reveal that Nell-1-combined AuNPs could be a promising
drug candidate for the prevention and treatment of periodontitis.
However, Nell-1-combined AuNPs did not show organ toxicity or impair
the integrity of intestinal epithelium but alter the gut microbiota,
leading to the dysbiosis of gut microbiota. The adverse impact of
changes in gut microbiota needs to be further investigated. Nonetheless,
this study provides a novel perspective and direction for the biological
safety assessment of biomaterials in oral clinical applications.