Kurarinone suppresses RANKL-induced osteoclastogenesis via calcineurin downregulation and NFATc1-GSK3β modulation
Su Ji Joo, Eun-Jae Park, Hye-Yeon Jung, Ju Jin Jeong, Na-Rae Kang, Sang-Wook Park, Ok Ran Lee, Seung Woong Lee, Tae-Hoon LeeBackground and purpose:
Osteoclasts play a critical role in bone resorption, and their excessive activity contributes to osteoporosis and other bone-related diseases. This study aimed to isolate and identify chromane and chromanone derivatives from
Experimental approach:
Five compounds were isolated from
Findings/Results:
Among the five compounds, kurarinone (C4) exhibited a significant inhibitory effect on RANKL-induced osteoclast differentiation. Kurarinone reduced the formation of multinucleated osteoclasts, suppressed F-actin ring formation, and decreased bone resorption activity. It downregulated the expression of osteoclast-specific genes by affecting the early phase of differentiation. Mechanistically, kurarinone dose-dependently decreased the expression of calcineurin A, suggesting suppression of NFATc1 activation via inhibition of its dephosphorylation.
Conclusion and implications:
Kurarinone is a promising natural compound that regulates osteoclast activity through downregulation of calcineurin A expression. These findings support its potential as a therapeutic agent for osteoporosis and other bone-related disorders.