Anti-Osteoporotic Effects of <i>n-trans</i>-Hibiscusamide and Its Derivative Alleviate Ovariectomy-Induced Bone Loss in Mice by Regulating RANKL-Induced Signaling
Osteoporosis is characterized by the deterioration of bone structures and decreased bone mass, leading to an increased risk of fracture. Estrogen deficiency in postmenopausal women and aging are major factors of osteoporosis and are some of the reasons for reduced quality of life. In this study, we...
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oai:doaj.org-article:1096cd9a3fea47bcb2254698825644be2021-11-25T18:27:28ZAnti-Osteoporotic Effects of <i>n-trans</i>-Hibiscusamide and Its Derivative Alleviate Ovariectomy-Induced Bone Loss in Mice by Regulating RANKL-Induced Signaling10.3390/molecules262268201420-3049https://doaj.org/article/1096cd9a3fea47bcb2254698825644be2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6820https://doaj.org/toc/1420-3049Osteoporosis is characterized by the deterioration of bone structures and decreased bone mass, leading to an increased risk of fracture. Estrogen deficiency in postmenopausal women and aging are major factors of osteoporosis and are some of the reasons for reduced quality of life. In this study, we investigated the effects of <i>n-trans</i>-hibiscusamide (NHA) and its derivative 4-<i>O</i>-(<i>E</i>)-feruloyl-<i>N</i>-(<i>E</i>)-hibiscusamide (HAD) on receptor activator of nuclear factor kappa-Β (NF-κB) ligand (RANKL)-induced osteoclast differentiation and an ovariectomized osteoporosis mouse model. NHA and HAD significantly inhibited the differentiation of osteoclasts from bone marrow-derived macrophages (BMMs) and the expression of osteoclast differentiation-related genes. At the molecular level, NHA and HAD significantly downregulated the phosphorylation of mitogen-activated protein kinase (MAPK) signaling molecules. However, Akt and NF-κB phosphorylation was inhibited only after NHA or HAD treatment. In the ovariectomy (OVX)-induced osteoporosis model, both NHA and HAD effectively improved trabecular bone structure. C-terminal telopeptide (CTX), a bone resorption marker, and RANKL, an osteoclast stimulation factor, were significantly reduced by NHA and HAD. The tartrate-resistant acid phosphatase (TRAP)-stained area, which indicates the osteoclast area, was also decreased by these compounds. These results show the potential of NHA and HAD as therapeutic agents for osteoporosis.Hyung Jin LimEun-Jae ParkYeong-Seon WonSeon Gyeong BakSun Hee CheongSeung Woong LeeSoyoung LeeSeung-Jae LeeMun-Chual RhoMDPI AGarticle<i>n-trans</i>-hibiscusamide4-<i>O</i>-(<i>E</i>)-feruloyl-<i>N-</i>(<i>E</i>)-hibiscusamideosteoclastogenesisOVX induced osteoporosisOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6820, p 6820 (2021) |
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DOAJ |
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EN |
topic |
<i>n-trans</i>-hibiscusamide 4-<i>O</i>-(<i>E</i>)-feruloyl-<i>N-</i>(<i>E</i>)-hibiscusamide osteoclastogenesis OVX induced osteoporosis Organic chemistry QD241-441 |
spellingShingle |
<i>n-trans</i>-hibiscusamide 4-<i>O</i>-(<i>E</i>)-feruloyl-<i>N-</i>(<i>E</i>)-hibiscusamide osteoclastogenesis OVX induced osteoporosis Organic chemistry QD241-441 Hyung Jin Lim Eun-Jae Park Yeong-Seon Won Seon Gyeong Bak Sun Hee Cheong Seung Woong Lee Soyoung Lee Seung-Jae Lee Mun-Chual Rho Anti-Osteoporotic Effects of <i>n-trans</i>-Hibiscusamide and Its Derivative Alleviate Ovariectomy-Induced Bone Loss in Mice by Regulating RANKL-Induced Signaling |
description |
Osteoporosis is characterized by the deterioration of bone structures and decreased bone mass, leading to an increased risk of fracture. Estrogen deficiency in postmenopausal women and aging are major factors of osteoporosis and are some of the reasons for reduced quality of life. In this study, we investigated the effects of <i>n-trans</i>-hibiscusamide (NHA) and its derivative 4-<i>O</i>-(<i>E</i>)-feruloyl-<i>N</i>-(<i>E</i>)-hibiscusamide (HAD) on receptor activator of nuclear factor kappa-Β (NF-κB) ligand (RANKL)-induced osteoclast differentiation and an ovariectomized osteoporosis mouse model. NHA and HAD significantly inhibited the differentiation of osteoclasts from bone marrow-derived macrophages (BMMs) and the expression of osteoclast differentiation-related genes. At the molecular level, NHA and HAD significantly downregulated the phosphorylation of mitogen-activated protein kinase (MAPK) signaling molecules. However, Akt and NF-κB phosphorylation was inhibited only after NHA or HAD treatment. In the ovariectomy (OVX)-induced osteoporosis model, both NHA and HAD effectively improved trabecular bone structure. C-terminal telopeptide (CTX), a bone resorption marker, and RANKL, an osteoclast stimulation factor, were significantly reduced by NHA and HAD. The tartrate-resistant acid phosphatase (TRAP)-stained area, which indicates the osteoclast area, was also decreased by these compounds. These results show the potential of NHA and HAD as therapeutic agents for osteoporosis. |
format |
article |
author |
Hyung Jin Lim Eun-Jae Park Yeong-Seon Won Seon Gyeong Bak Sun Hee Cheong Seung Woong Lee Soyoung Lee Seung-Jae Lee Mun-Chual Rho |
author_facet |
Hyung Jin Lim Eun-Jae Park Yeong-Seon Won Seon Gyeong Bak Sun Hee Cheong Seung Woong Lee Soyoung Lee Seung-Jae Lee Mun-Chual Rho |
author_sort |
Hyung Jin Lim |
title |
Anti-Osteoporotic Effects of <i>n-trans</i>-Hibiscusamide and Its Derivative Alleviate Ovariectomy-Induced Bone Loss in Mice by Regulating RANKL-Induced Signaling |
title_short |
Anti-Osteoporotic Effects of <i>n-trans</i>-Hibiscusamide and Its Derivative Alleviate Ovariectomy-Induced Bone Loss in Mice by Regulating RANKL-Induced Signaling |
title_full |
Anti-Osteoporotic Effects of <i>n-trans</i>-Hibiscusamide and Its Derivative Alleviate Ovariectomy-Induced Bone Loss in Mice by Regulating RANKL-Induced Signaling |
title_fullStr |
Anti-Osteoporotic Effects of <i>n-trans</i>-Hibiscusamide and Its Derivative Alleviate Ovariectomy-Induced Bone Loss in Mice by Regulating RANKL-Induced Signaling |
title_full_unstemmed |
Anti-Osteoporotic Effects of <i>n-trans</i>-Hibiscusamide and Its Derivative Alleviate Ovariectomy-Induced Bone Loss in Mice by Regulating RANKL-Induced Signaling |
title_sort |
anti-osteoporotic effects of <i>n-trans</i>-hibiscusamide and its derivative alleviate ovariectomy-induced bone loss in mice by regulating rankl-induced signaling |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doaj.org/article/1096cd9a3fea47bcb2254698825644be |
work_keys_str_mv |
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