<i>Eleutherococcus sessiliflorus</i> Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Induced Bone Loss
The aim of this study was to evaluate the effects of root bark of <i>Eleutherococcus sessiliflorus</i> (ES) on osteoclast differentiation and function in vitro and in vivo. In vitro, we found that ES significantly inhibited the RANKL-induced formation of TRAP-positive multinucleated oste...
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MDPI AG
2021-03-01
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| Online Access: | https://www.mdpi.com/1420-3049/26/7/1886 |
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| author | Sang-Yong Han June-Hyun Kim Eun-Heui Jo Yun-Kyung Kim |
| author_facet | Sang-Yong Han June-Hyun Kim Eun-Heui Jo Yun-Kyung Kim |
| author_sort | Sang-Yong Han |
| collection | DOAJ |
| description | The aim of this study was to evaluate the effects of root bark of <i>Eleutherococcus sessiliflorus</i> (ES) on osteoclast differentiation and function in vitro and in vivo. In vitro, we found that ES significantly inhibited the RANKL-induced formation of TRAP-positive multinucleated osteoclasts and osteoclastic bone resorption without cytotoxic effects. ES markedly downregulated the expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1); c-Fos; and osteoclast-related marker genes, such as TRAP, osteoclast-associated receptor (OSCAR), matrix metalloproteinase-9 (MMP-9), calcitonin receptor, cathepsin K, the 38 kDa d2 subunit of the vacuolar H<sup>+</sup>-transporting lysosomal ATPase (Atp6v0d2), dendritic cell-specific transmembrane protein (DC-STAMP), and osteoclast-stimulatory transmembrane protein (OC-STAMP). These effects were achieved by inhibiting the RANKL-mediated activation of MAPK signaling pathway proteins, including p38, ERK, and JNK. In vivo, ES attenuated OVX-induced decrease in bone volume to tissue volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and bone mineral density, but increased trabecular separation (Tb.Sp) in the femur. Collectively, our findings showed that ES inhibited RANKL-activated osteoclast differentiation in bone marrow macrophages and prevented OVX-mediated bone loss in rats. These findings suggest that ES has the potential to be used as a therapeutic agent for bone-related diseases, such as osteoporosis. |
| first_indexed | 2024-03-10T12:52:25Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T12:52:25Z |
| publishDate | 2021-03-01 |
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| series | Molecules |
| spelling | doaj.art-9bde8a0072654d23b90f3e3f265551ff2023-11-21T12:11:51ZengMDPI AGMolecules1420-30492021-03-01267188610.3390/molecules26071886<i>Eleutherococcus sessiliflorus</i> Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Induced Bone LossSang-Yong Han0June-Hyun Kim1Eun-Heui Jo2Yun-Kyung Kim3Department of Herbal Medicine, College of Pharmacy, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaDepartment of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaDepartment of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaDepartment of Herbal Medicine, College of Pharmacy, Wonkwang University, 460 Iksandae-ro, Iksan, Jeonbuk 54538, KoreaThe aim of this study was to evaluate the effects of root bark of <i>Eleutherococcus sessiliflorus</i> (ES) on osteoclast differentiation and function in vitro and in vivo. In vitro, we found that ES significantly inhibited the RANKL-induced formation of TRAP-positive multinucleated osteoclasts and osteoclastic bone resorption without cytotoxic effects. ES markedly downregulated the expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1); c-Fos; and osteoclast-related marker genes, such as TRAP, osteoclast-associated receptor (OSCAR), matrix metalloproteinase-9 (MMP-9), calcitonin receptor, cathepsin K, the 38 kDa d2 subunit of the vacuolar H<sup>+</sup>-transporting lysosomal ATPase (Atp6v0d2), dendritic cell-specific transmembrane protein (DC-STAMP), and osteoclast-stimulatory transmembrane protein (OC-STAMP). These effects were achieved by inhibiting the RANKL-mediated activation of MAPK signaling pathway proteins, including p38, ERK, and JNK. In vivo, ES attenuated OVX-induced decrease in bone volume to tissue volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and bone mineral density, but increased trabecular separation (Tb.Sp) in the femur. Collectively, our findings showed that ES inhibited RANKL-activated osteoclast differentiation in bone marrow macrophages and prevented OVX-mediated bone loss in rats. These findings suggest that ES has the potential to be used as a therapeutic agent for bone-related diseases, such as osteoporosis.https://www.mdpi.com/1420-3049/26/7/1886<i>Eleutherococcus sessiliflorus</i>OsteoporosisRANKLOsteoclast differentiationNFATc1c-Fos |
| spellingShingle | Sang-Yong Han June-Hyun Kim Eun-Heui Jo Yun-Kyung Kim <i>Eleutherococcus sessiliflorus</i> Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Induced Bone Loss Molecules <i>Eleutherococcus sessiliflorus</i> Osteoporosis RANKL Osteoclast differentiation NFATc1 c-Fos |
| title | <i>Eleutherococcus sessiliflorus</i> Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Induced Bone Loss |
| title_full | <i>Eleutherococcus sessiliflorus</i> Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Induced Bone Loss |
| title_fullStr | <i>Eleutherococcus sessiliflorus</i> Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Induced Bone Loss |
| title_full_unstemmed | <i>Eleutherococcus sessiliflorus</i> Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Induced Bone Loss |
| title_short | <i>Eleutherococcus sessiliflorus</i> Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Induced Bone Loss |
| title_sort | i eleutherococcus sessiliflorus i inhibits receptor activator of nuclear factor kappa b ligand rankl induced osteoclast differentiation and prevents ovariectomy ovx induced bone loss |
| topic | <i>Eleutherococcus sessiliflorus</i> Osteoporosis RANKL Osteoclast differentiation NFATc1 c-Fos |
| url | https://www.mdpi.com/1420-3049/26/7/1886 |
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