Publication: Cyperenoic acid suppresses osteoclast differentiation and delays bone loss in a senile osteoporosis mouse model by inhibiting non-canonical NF-κB pathway
Issued Date
2018-12-01
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ISSN
20452322
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2-s2.0-85044978366
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Mahidol University
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SCOPUS
Bibliographic Citation
Scientific Reports. Vol.8, No.1 (2018)
Suggested Citation
Supatta Chawalitpong, Ratchanaporn Chokchaisiri, Apichart Suksamrarn, Shigeru Katayama, Takakazu Mitani, Soichiro Nakamura, Ahmad Ai Athamneh, Patcharee Ritprajak, Asada Leelahavanichkul, Ratchaneevan Aeimlapa, Narattaphol Charoenphandhu, Tanapat Palaga Cyperenoic acid suppresses osteoclast differentiation and delays bone loss in a senile osteoporosis mouse model by inhibiting non-canonical NF-κB pathway. Scientific Reports. Vol.8, No.1 (2018). doi:10.1038/s41598-018-23912-3 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/47493
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Title
Cyperenoic acid suppresses osteoclast differentiation and delays bone loss in a senile osteoporosis mouse model by inhibiting non-canonical NF-κB pathway
Abstract
© 2018 The Author(s). Cyperenoic acid is a terpenoid isolated from the root of a medicinal plant Croton crassifolius with a wide range of biological activities. In this study, the effects of cyperenoic acid on osteoclast differentiation were investigated both in vitro and in vivo using receptor activator of nuclear factor-κB ligand (RANKL)-induced bone marrow-derived osteoclasts and senescence-accelerated mouse prone 6 (SAMP6). Cyperenoic acid significantly suppressed RANKL-induced osteoclast differentiation at the concentrations with no apparent cytotoxicity. The half maximum inhibitory concentration (IC50) for osteoclast differentiation was 36.69 μM ± 1.02. Cyperenoic acid treatment evidently reduced the expression of two key transcription factors in osteoclast differentiation, NFATc1 and c-Fos. Detailed signaling analysis revealed that cyperenoic acid did not affect MAPK pathways and canonical NF-κB pathway but impaired activation of p100/p52 in the non-canonical NF-κB pathway upon RANKL stimulation. Moreover, the expression of osteoclast-related genes, nfatc1, ctsk, irf8, acp5 and cfos were disrupted by cyperenoic acid treatment. The bone resorption activity by cyperenoic acid-treated osteoclasts were impaired. In a senile osteoporosis mouse model SAMP6, mice fed on diet supplemented with cyperenoic acid showed delay in bone loss, compared to the control. Taken together, plant-derived cyperenoic acid shows great potential as therapeutic agent for osteoporosis.