In vitro effects of ursolic acid on RANKL-induced osteoclast differentiation

Purpose: Ursolic acid is a small pentacyclic triterpene molecule composed of isoprenoid units. Although ursolic acid has been shown to be effective in the treatment of rheumatoid arthritis in many studies, very little research has been conducted on bone diseases caused by bone loss. The present study aimed to evaluate the effects of ursolic acid on osteoclast formation with the aim of finding herbal medicines that inhibit osteoclast function to strengthen bones and promote vitality in old age. Materials and Methods: RAW264.7 murine macrophages were used in our study and cells were treated with 100 ng/mL RANKL for osteoclastic differentiation. The effects of ursolic acid treatment on cell viability, tartrate-resistant acid phosphatase (TRAP) formation and osteoclastic gene expression levels were then measured. Results: Our results showed that ursolic acid did not exhibit significant cytotoxicity (3.2-9.8%) at concentrations of 2.5-10 mu g/mL. Furthermore, ursolic acid inhibited osteoclast differentiation (15.2-39.1%) and suppressed the expression of osteoclastic genes such as cathepsin K (3.8-22.3%), TRAP (16.3-48. 7%), matrix metalloproteinase-9 ( MMP-9 ) (10.7-40.2%), nuclear factor of activated T-cell cytoplasmic 1 ( NFATc1 ) (1.2-29.7%), cFos (0.9-13.8%) and microphthalmia-associated transcription factor ( MITF ) (2.2-21.6%). Conclusion: Ursolic acid has been shown to inhibit RANKL-induced osteoclast differentiation and therefore we believe that ursolic acid may be used for the treatment and prevention of osteoporosis.