BETULINIC ACID INHIBITS RANKL-INDUCED OSTEOCLASTOGENESIS VIA ATTENUATING AKT, NF-KB, AND PLCG2-CA2+ SIGNALING AND PREVENTS INFLAMMATORY BONE LOSS

Background: Betulinic acid (BA), a natural plant-derived pentacyclic triterpenoid compound, is known to possess numerous pharmacological and biochemical properties including anti-inflammatory, anti-cancer, and anti-adipogenic activity. Objectives: we investigated that BA could suppress RANKL-induced osteoclastogenesis and bone resorption. Results: BA significantly suppressed osteoclastogenesis by decreasing the phosphorylation of Akt and IkB, as well as PLCγ2-Ca signaling, in pathways involved in early osteoclastogenesis as well as through the subsequent suppression of c-Fos and NFATc1. The inhibition of these pathways by BA was once more confirmed by retrovirus infection of constitutively active (CA)-Akt and CA-Ikkβ retrovirus and measurement of Ca influx. BA also significantly inhibited the expression of osteoclastogenesis-specific marker genes. Moreover, we found that BA administration restored the bone loss induced through acute lipopolysaccharide injection in mice by a micro-CT and histological analysis. Conclusion: Our findings suggest that BA is a potential therapeutic candidate for bone diseases involving osteoclasts. Disclosure of Interests: None declared Citation: Ann Rheum Dis, volume 79, supplement 1, year 2020, page 778Session: Bone diseases, including osteoporosis and osteoimmunology: aetiology, pathology and animal models (Poster Presentations)