ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1822

Oleanolic Acid Acetate Inhibits Osteoclast Differentiation By Downregulating Phospholipase Cγ2 –calcium ion oscillation-Nuclear Factor Of Activated T Cell c1 Signaling, and Suppresses Bone Loss In Mice

Chang-Hoon Lee1, Myeung Su Lee1, Won Seok Lee2, Wan-Hee Yoo3, Ju-Young Kim4, Jae-Min Oh4 and Yong-Geun Jeong5, 1Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Chonbuk, South Korea, 2Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, Jeonju, South Korea, 3Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, Jeonju, South Korea, 4Department of Anatomy, School of Medicine, Wonkwang University, Iksan, South Korea, 5Division of Rheumatology, Department of Internal Medicine, Changwon Fatima Hospital, Changwon, South Korea

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Biology and Pathology of Bone and Joint (Bone and Arthritis)

Session Type: Abstract Submissions (ACR)

Background/Purpose: 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. angularisextract, but the pharmacological effect is not known. Therefore, we investigated the effect and mechanism of OAA in receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclast differentiation and bone resorption.

Methods: V. angularis was obtained from an herbal medicine store (Jeonbuk, Korea). The plant material (10 kg) was dried, ground to a fine powder, and extracted with 95% ethanol at 70°C. The extracts were filtered through a 0.45-mm filter and concentrated under reduced pressure to yield the ethanol extracts, which were further extracted with ethyl acetate. we treated primary BMMs with various concentrations of OAA in the presence of RANKL and M-CSF. Expression of c-Fos, NFATc1, TRAP and OSCAR were determined by RT-PCR and Western blot analysis. we used a retrovirus to overexpress NFATc1 and the CA form of NFATc1 (CA-NFATc1) in BMMs and examined the effect of OAA on the MAPKs and Ca2+ responses in the presence of RANKL. To investigate whether OAA affects bone-resorbing activity, mature osteoclasts were cultured on hydroxyapatite-coated plates. Finally, We investigated the in vivo effects of OAA with an experimental animal model of bone erosion. Mice were intraperitoneally injected with LPS with or without OAA. The mice were sacrificed 8 days after the first LPS injection, and the left femurs underwent micro-CT analyses.

Results: Interestingly, OAA significantly inhibited phospholipase Cγ2 (PLCg2) phosphorylation, calcium ion (Ca2+) 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.

Conclusion: Taken together, the results suggested that OAA inhibited RANKL-mediated osteoclastogenesis via PLCg2–Ca2+-NFATc1 signaling in vitro and suppressed inflammatory bone loss in vivo.

Disclosure:

C. H. Lee,
None;

M. S. Lee,
None;

W. S. Lee,
None;

W. H. Yoo,
None;

J. Y. Kim,
None;

J. M. Oh,
None;

Y. G. Jeong,
None.

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/oleanolic-acid-acetate-inhibits-osteoclast-differentiation-by-downregulating-phospholipase-c%ce%b32-calcium-ion-oscillation-nuclear-factor-of-activated-t-cell-c1-signaling-and-suppresse/