3-Hydroxyolean-12-en-27-oic Acids Inhibit RANKL-Induced Osteoclastogenesis in Vitro and Inflammation-Induced Bone Loss in Vivo
Olean-12-en-27-oic acids possess a variety of pharmacological effects. However, their effects and underlying mechanisms on osteoclastogenesis remain unclear. This study aimed to investigate the anti-osteoclastogenic effects of five olean-12-en-27-oic acid derivatives including 3α,23-isopropylidenedi...
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/15/5240 |
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| author | Wonyoung Seo Suhyun Lee Phuong Thao Tran Thi Quynh-Mai Ngo Okwha Kim Thanh Huong Le Nguyen Hai Dang Cheol Hwangbo Byung Sun Min Jeong-Hyung Lee |
| author_facet | Wonyoung Seo Suhyun Lee Phuong Thao Tran Thi Quynh-Mai Ngo Okwha Kim Thanh Huong Le Nguyen Hai Dang Cheol Hwangbo Byung Sun Min Jeong-Hyung Lee |
| author_sort | Wonyoung Seo |
| collection | DOAJ |
| description | Olean-12-en-27-oic acids possess a variety of pharmacological effects. However, their effects and underlying mechanisms on osteoclastogenesis remain unclear. This study aimed to investigate the anti-osteoclastogenic effects of five olean-12-en-27-oic acid derivatives including 3α,23-isopropylidenedioxyolean-12-en-27-oic acid (AR-1), 3-oxoolean-12-en-27-oic acid (AR-2), 3α-hydroxyolean-12-en-27-oic acid (AR-3), 23-hydroxy-3-oxoolean-12-en-27-oic acid (AR-4), and aceriphyllic acid A (AR-5). Among the five olean-12-en-27-oic acid derivatives, 3-hydroxyolean-12-en-27-oic acid derivatives, AR-3 and AR-5, significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced mature osteoclast formation by reducing the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, F–actin ring formation, and mineral resorption activity. AR-3 and AR-5 decreased RANKL-induced expression levels of osteoclast-specific marker genes such as c-Src, TRAP, and cathepsin K (CtsK) as well as c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). Mice treated with either AR-3 or AR-5 showed significant protection of the mice from lipopolysaccharide (LPS)-induced bone destruction and osteoclast formation. In particular, AR-5 suppressed RANKL-induced phosphorylation of JNK and ERK mitogen-activated protein kinases (MAPKs). The results suggest that AR-3 and AR-5 attenuate osteoclast formation in vitro and in vivo by suppressing RANKL-mediated MAPKs and NFATc1 signaling pathways and could potentially be lead compounds for the prevention or treatment of osteolytic bone diseases. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:14:40Z |
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| spelling | doaj.art-1bf89a38e0d54b6c8c855b1221ec9e932023-11-20T07:45:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012115524010.3390/ijms211552403-Hydroxyolean-12-en-27-oic Acids Inhibit RANKL-Induced Osteoclastogenesis in Vitro and Inflammation-Induced Bone Loss in VivoWonyoung Seo0Suhyun Lee1Phuong Thao Tran2Thi Quynh-Mai Ngo3Okwha Kim4Thanh Huong Le5Nguyen Hai Dang6Cheol Hwangbo7Byung Sun Min8Jeong-Hyung Lee9Department of Biochemistry, Kangwon National University, Chuncheon, Gangwon-Do 24341, KoreaDepartment of Biochemistry, Kangwon National University, Chuncheon, Gangwon-Do 24341, KoreaDepartment of Biochemistry, Kangwon National University, Chuncheon, Gangwon-Do 24341, KoreaCollege of Pharmacy, Catholic University of Daegu, Gyeongbuk 38430, KoreaDepartment of Biochemistry, Kangwon National University, Chuncheon, Gangwon-Do 24341, KoreaUniversity of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Caugiay, Hanoi 100000, VietnamUniversity of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Caugiay, Hanoi 100000, VietnamDivision of Applied Life Science (BK21 Plus), PMBBRC, Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 52828, KoreaCollege of Pharmacy, Catholic University of Daegu, Gyeongbuk 38430, KoreaDepartment of Biochemistry, Kangwon National University, Chuncheon, Gangwon-Do 24341, KoreaOlean-12-en-27-oic acids possess a variety of pharmacological effects. However, their effects and underlying mechanisms on osteoclastogenesis remain unclear. This study aimed to investigate the anti-osteoclastogenic effects of five olean-12-en-27-oic acid derivatives including 3α,23-isopropylidenedioxyolean-12-en-27-oic acid (AR-1), 3-oxoolean-12-en-27-oic acid (AR-2), 3α-hydroxyolean-12-en-27-oic acid (AR-3), 23-hydroxy-3-oxoolean-12-en-27-oic acid (AR-4), and aceriphyllic acid A (AR-5). Among the five olean-12-en-27-oic acid derivatives, 3-hydroxyolean-12-en-27-oic acid derivatives, AR-3 and AR-5, significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced mature osteoclast formation by reducing the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, F–actin ring formation, and mineral resorption activity. AR-3 and AR-5 decreased RANKL-induced expression levels of osteoclast-specific marker genes such as c-Src, TRAP, and cathepsin K (CtsK) as well as c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). Mice treated with either AR-3 or AR-5 showed significant protection of the mice from lipopolysaccharide (LPS)-induced bone destruction and osteoclast formation. In particular, AR-5 suppressed RANKL-induced phosphorylation of JNK and ERK mitogen-activated protein kinases (MAPKs). The results suggest that AR-3 and AR-5 attenuate osteoclast formation in vitro and in vivo by suppressing RANKL-mediated MAPKs and NFATc1 signaling pathways and could potentially be lead compounds for the prevention or treatment of osteolytic bone diseases.https://www.mdpi.com/1422-0067/21/15/52403-hydroxyolean-12-en-27-oic acidosteoclastogenesisRANKLc-FosNFATc1 |
| spellingShingle | Wonyoung Seo Suhyun Lee Phuong Thao Tran Thi Quynh-Mai Ngo Okwha Kim Thanh Huong Le Nguyen Hai Dang Cheol Hwangbo Byung Sun Min Jeong-Hyung Lee 3-Hydroxyolean-12-en-27-oic Acids Inhibit RANKL-Induced Osteoclastogenesis in Vitro and Inflammation-Induced Bone Loss in Vivo International Journal of Molecular Sciences 3-hydroxyolean-12-en-27-oic acid osteoclastogenesis RANKL c-Fos NFATc1 |
| title | 3-Hydroxyolean-12-en-27-oic Acids Inhibit RANKL-Induced Osteoclastogenesis in Vitro and Inflammation-Induced Bone Loss in Vivo |
| title_full | 3-Hydroxyolean-12-en-27-oic Acids Inhibit RANKL-Induced Osteoclastogenesis in Vitro and Inflammation-Induced Bone Loss in Vivo |
| title_fullStr | 3-Hydroxyolean-12-en-27-oic Acids Inhibit RANKL-Induced Osteoclastogenesis in Vitro and Inflammation-Induced Bone Loss in Vivo |
| title_full_unstemmed | 3-Hydroxyolean-12-en-27-oic Acids Inhibit RANKL-Induced Osteoclastogenesis in Vitro and Inflammation-Induced Bone Loss in Vivo |
| title_short | 3-Hydroxyolean-12-en-27-oic Acids Inhibit RANKL-Induced Osteoclastogenesis in Vitro and Inflammation-Induced Bone Loss in Vivo |
| title_sort | 3 hydroxyolean 12 en 27 oic acids inhibit rankl induced osteoclastogenesis in vitro and inflammation induced bone loss in vivo |
| topic | 3-hydroxyolean-12-en-27-oic acid osteoclastogenesis RANKL c-Fos NFATc1 |
| url | https://www.mdpi.com/1422-0067/21/15/5240 |
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