3-Hydroxyolean-12-en-27-oic Acids Inhibit RANKL-Induced Osteoclastogenesis in Vitro and Inflammation-Induced Bone Loss in Vivoopen access
- Seo, Wonyoung; Lee, Suhyun; Phuong Thao Tran; Thi Quynh-Mai Ngo; Kim, Okwha; Thanh Huong Le; Nguyen Hai Dang; Hwangbo, Cheol; Min, Byung Sun; Lee, Jeong-Hyung
- Issue Date
- 3-hydroxyolean-12-en-27-oic acid; osteoclastogenesis; RANKL; c-Fos; NFATc1
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.21, no.15
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- 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 3 alpha,23-isopropylidenedioxyolean-12-en-27-oic acid (AR-1), 3-oxoolean-12-en-27-oic acid (AR-2), 3 alpha-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-kappa B 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
- ETC > Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.