Oleanolic acid acetate inhibits osteoclast differentiation by downregulating PLCγ2-Ca(2+)-NFATc1 signaling, and suppresses bone loss in mice.

Publisher: Elsevier Science Country of Publication: United States NLM ID: 8504048 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2763 (Electronic) Linking ISSN: 18732763 NLM ISO Abbreviation: Bone Subsets: MEDLINE

Publication: New York : Elsevier Science
Original Publication: Elmsford, NY : Pergamon Press, c1985-

Bone Resorption/*drug therapy ; Calcium/*metabolism ; Cell Differentiation/*drug effects ; Down-Regulation/*drug effects ; NFATC Transcription Factors/*metabolism ; Oleanolic Acid/*analogs & derivatives ; Oleanolic Acid/*therapeutic use ; Phospholipase C gamma/*metabolism; Animals ; Bone Marrow Cells/drug effects ; Bone Marrow Cells/metabolism ; Bone Marrow Cells/pathology ; Bone Resorption/enzymology ; Bone Resorption/metabolism ; Bone Resorption/pathology ; Humans ; Lipopolysaccharides ; Macrophages/drug effects ; Macrophages/metabolism ; Macrophages/pathology ; Male ; Mice ; Mice, Inbred ICR ; Oleanolic Acid/administration & dosage ; Oleanolic Acid/pharmacology ; Osteoclasts/drug effects ; Osteoclasts/enzymology ; Osteoclasts/metabolism ; Osteoclasts/pathology ; RANK Ligand/pharmacology ; Signal Transduction/drug effects

Owing to their potential pharmacological activities in human disease, natural plant-derived compounds have recently become the focus of increased research interest. In this study, we first isolated oleanolic acid acetate (OAA), a triterpenoid compound, from Vigna angularis (azuki bean) to discover anti-bone resorptive agents. Many studies have identified and described the various medicinal effects of V. angularis extract. However, the pharmacological effect of OAA-derived V. angularis extract, particularly the effect on osteoclastogenesis, is not known. Therefore, we investigated the effect and mechanism of OAA in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. OAA inhibited RANKL-induced osteoclast differentiation in bone marrow macrophages (BMMs) without any evidence of cytotoxicity. Interestingly, OAA significantly inhibited Btk phosphorylation, phospholipase Cγ2 (PLCγ2) phosphorylation, calcium ion (Ca(2+)) oscillation, and nuclear factor of activated T cell c1 (NFATc1) expression in RANKL-stimulated BMMs, but did not affect RANKL-induced mitogen-activated protein kinase. OAA also inhibited the bone-resorbing activity of mature osteoclasts. Furthermore, mice treated with OAA demonstrated marked attenuation of lipopolysaccharide-induced bone erosion based on micro-computed tomography and histologic analysis of femurs. Taken together, the results suggested that OAA inhibited RANKL-mediated osteoclastogenesis via PLCγ2-Ca(2+)-NFATc1 signaling in vitro and suppressed inflammatory bone loss in vivo.
(Copyright © 2013. Published by Elsevier Inc.)

Keywords: Calcium oscillation; NFATc1; Oleanolic acid acetate; Osteoclast; PLCγ2

0 (Lipopolysaccharides)
0 (NFATC Transcription Factors)
0 (RANK Ligand)
6SMK8R7TGJ (Oleanolic Acid)
EC 3.1.4.3 (Phospholipase C gamma)
SY7Q814VUP (Calcium)

Date Created: 20131224 Date Completed: 20141021 Latest Revision: 20140217

20221213

10.1016/j.bone.2013.12.013

24361669