Therapeutic potential of farnesoid X receptor agonists for modulating inflammation and periodontal regeneration.

Abstract

Inflammation and osteoclast activity are important in various diseases, including periodontitis and osteoporosis. Farnesoid X receptor (FXR) has been identified as a promising target for modulating these processes. This study delved into the impact of FXR agonists on inflammation and periodontal regeneration using periodontitis models. The RAW264.7 and gingival fibroblast cells were divided into five groups: control, lipopolysaccharide (LPS), LPS combined with FXR agonist, LPS with si-FXR, and LPS with si-FXR alongside FXR agonist. FXR expression and pro-inflammatory cytokine levels were quantified. Osteoclast activity was evaluated by observing morphological alterations and tartrate-resistant acid phosphatase staining. The rats were used to establish periodontitis models and received varying doses of FXR agonist. Bone health metrics were assessed, and the expressions of runt-related transcription factor 2 (RUNX2), integrin-binding sialoprotein (IBSP), nuclear factor-kappa B (NF-kB), phosphorylated nuclear factor-kappa B (p-NF-kB), toll-like receptor 4 (TLR4), and toll-like receptor 2 (TLR2) were determined. FXR suppressed the release of pro-inflammatory cytokines in both LPS-stimulated RAW264.7 and gingival fibroblast cells, while curbing osteoclastogenesis. In periodontitis rat models, FXR agonist administration caused notable enhancement in bone density. Moreover, FXR agonist mitigated periodontal inflammation, decreased periodontal index markers and suppressed the expressions of NF-kB, p-NF-kB, TLR4, and TLR2, but upregulated the expressions of RUNX2 and IBSP. The data underscores the potential of FXR agonists in attenuating inflammation and periodontal regeneration, both in vitro and in vivo. This suggests the potential therapeutic application of FXR agonists in conditions marked by inflammation and bone degradation.