| RRC ID |
64036
|
| Author |
Chawalitpong S, Chokchaisiri R, Suksamrarn A, Katayama S, Mitani T, Nakamura S, Athamneh AA, Ritprajak P, Leelahavanichkul A, Aeimlapa R, Charoenphandhu N, Palaga T.
|
| Title |
Cyperenoic acid suppresses osteoclast differentiation and delays bone loss in a senile osteoporosis mouse model by inhibiting non-canonical NF-κB pathway.
|
| Journal |
Sci Rep
|
| Abstract |
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.
|
| Volume |
8(1)
|
| Pages |
5625
|
| Published |
2018-4-4
|
| DOI |
10.1038/s41598-018-23912-3
|
| PII |
10.1038/s41598-018-23912-3
|
| PMID |
29618833
|
| PMC |
PMC5884777
|
| MeSH |
Animals
Bone Resorption / etiology
Bone Resorption / prevention & control*
Cell Differentiation / drug effects*
Cells, Cultured
Disease Models, Animal*
Female
Mice
Mice, Inbred BALB C
NF-kappa B / antagonists & inhibitors*
Osteoclasts / drug effects*
Osteoclasts / metabolism
Osteoclasts / pathology
Osteoporosis / complications
Osteoporosis / drug therapy*
Sesquiterpenes / pharmacology*
|
| IF |
3.968
|
| Resource |
| Human and Animal Cells |
MC3T3-E1(RCB1126) |
