Next Article in Journal
Irradiation-Induced Upregulation of miR-711 Inhibits DNA Repair and Promotes Neurodegeneration Pathways
Previous Article in Journal
Interleukin-6 in Rheumatoid Arthritis
Open AccessArticle

3-Hydroxyolean-12-en-27-oic Acids Inhibit RANKL-Induced Osteoclastogenesis in Vitro and Inflammation-Induced Bone Loss in Vivo

1
Department of Biochemistry, Kangwon National University, Chuncheon, Gangwon-Do 24341, Korea
2
Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon, Gangwon-Do 24341, Korea
3
College of Pharmacy, Catholic University of Daegu, Gyeongbuk 38430, Korea
4
University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Caugiay, Hanoi 100000, Vietnam
5
Division of Applied Life Science (BK21 Plus), PMBBRC, Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 52828, Korea
*
Author to whom correspondence should be addressed.
These authors equally contributed to this work.
Int. J. Mol. Sci. 2020, 21(15), 5240; https://doi.org/10.3390/ijms21155240
Received: 18 June 2020 / Revised: 17 July 2020 / Accepted: 22 July 2020 / Published: 23 July 2020
(This article belongs to the Section Bioactives and Nutraceuticals)
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. View Full-Text
Keywords: 3-hydroxyolean-12-en-27-oic acid; osteoclastogenesis; RANKL; c-Fos; NFATc1 3-hydroxyolean-12-en-27-oic acid; osteoclastogenesis; RANKL; c-Fos; NFATc1
Show Figures

Graphical abstract

MDPI and ACS Style

Seo, W.; Lee, S.; Tran, P.T.; Ngo, T. .-M.; Kim, O.; Le, T.H.; Dang, N.H.; Hwangbo, C.; Min, B.S.; Lee, J.-H. 3-Hydroxyolean-12-en-27-oic Acids Inhibit RANKL-Induced Osteoclastogenesis in Vitro and Inflammation-Induced Bone Loss in Vivo. Int. J. Mol. Sci. 2020, 21, 5240.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop