Antcin K suppresses osteoclastogenesis through modulation of the focal adhesion kinase and phosphoinositide 3-kinase pathways and attenuates ligature-induced periodontitis.

BACKGROUND/PURPOSE: Periodontitis is a chronic inflammatory condition characterized by host-mediated destruction of periodontal tissue and alveolar bone. Elevated proinflammatory cytokines and osteoclast activation are key factors contributing to this breakdown. Antcin K, a triterpenoid derived from Antrodia cinnamomea, exhibits immunomodulatory and anti-inflammatory properties. This study aimed to investigate whether Antcin K suppresses osteoclast formation and prevents the progression of periodontitis. MATERIALS AND METHODS: Receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in murine macrophage cell line RAW 264.7 cells was evaluated following Antcin K treatment. RNA sequencing and pathway analysis revealed the involvement of the focal adhesion kinase (FAK)-phosphoinositide 3-kinase (PI3K) signaling axis, which was further validated by Western blotting. In vivo, a ligature-induced periodontitis rat model was used to assess osteoclast activity, RANKL/osteoprotegerin (OPG) expression, and alveolar bone preservation following Antcin K treatment. RESULTS: Antcin K significantly suppressed RANKL-induced osteoclast formation in vitro. Transcriptomic and biochemical analyses indicated that inhibition of the FAK-PI3K signaling cascade mediates its suppressive effect. In vivo, Antcin K reduced osteoclast numbers, lowered the RANKL/OPG ratio, and alleviated alveolar bone resorption in ligature-induced periodontitis. CONCLUSION: Antcin K inhibits osteoclastogenesis by modulating the FAK-PI3K signaling pathway and attenuates alveolar bone loss. These findings suggest that Antcin K may serve as a potential host-modulatory therapeutic agent for the treatment of periodontitis.