2. Academic Validation
  3. Eudebeiolide B Inhibits Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Regulating RANKL-Induced NF-κB, c-Fos and Calcium Signaling

Eudebeiolide B Inhibits Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Regulating RANKL-Induced NF-κB, c-Fos and Calcium Signaling

  • Pharmaceuticals (Basel). 2020 Dec 16;13(12):468. doi: 10.3390/ph13120468.
Mi-Hwa Kim 1,  Hyung-Jin Lim 2,  Seon Gyeong Bak 2,  Eun-Jae Park 2,  Hyun-Jae Jang 3,  Seung Woong Lee 2,  Soyoung Lee 2,  Kang Min Lee 4,  Sun Hee Cheong 5,  Seung-Jae Lee 2,  Mun-Chual Rho 2
Affiliations

Affiliations

  • 1 Biological Resources Research Group, Gyeongnam Department of Environment Toxicology and Chemistry, Korea Institute of Toxicology (KIT), Jinju 52834, Korea.
  • 2 Immunoregulatory Material Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 56212, Korea.
  • 3 Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Korea.
  • 4 Department of Molecular Biology, Chonbuk National University, Jeonju 54896, Korea.
  • 5 Department of Marine Bio Food Science, Chonnam National University, Yeosu 59626, Korea.
PMID: 33339187 DOI: 10.3390/ph13120468
Abstract

Eudebeiolide B is a eudesmane-type sesquiterpenoid compound isolated from Salvia plebeia R. Br., and little is known about its biological activity. In this study, we investigated the effects of eudebeiolide B on osteoblast differentiation, receptor activator nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro and ovariectomy-induced bone loss in vivo. Eudebeiolide B induced the expression of Alkaline Phosphatase (ALP) and calcium accumulation during MC3T3-E1 osteoblast differentiation. In mouse bone marrow macrophages (BMMs), eudebeiolide B suppressed RANKL-induced osteoclast differentiation of BMMs and bone resorption. Eudebeiolide B downregulated the expression of nuclear factor of activated T-cells 1 (NFATc1) and c-fos, transcription factors induced by RANKL. Moreover, eudebeiolide B attenuated the RANKL-induced expression of osteoclastogenesis-related genes, including Cathepsin K (Ctsk), matrix metalloproteinase 9 (MMP9) and dendrocyte expressed seven transmembrane protein (DC-STAMP). Regarding the molecular mechanism, eudebeiolide B inhibited the phosphorylation of Akt and NF-κB p65. In addition, it downregulated the expression of cAMP response element-binding protein (CREB), Bruton's tyrosine kinase (Btk) and Phospholipase Cγ2 (PLCγ2) in RANKL-induced calcium signaling. In an ovariectomized (OVX) mouse model, intragastric injection of eudebeiolide B prevented OVX-induced bone loss, as shown by bone mineral density and contents, microarchitecture parameters and serum levels of bone turnover markers. Eudebeiolide B not only promoted osteoblast differentiation but inhibited RANKL-induced osteoclastogenesis through calcium signaling and prevented OVX-induced bone loss. Therefore, eudebeiolide B may be a new therapeutic agent for osteoclast-related diseases, including osteoporosis, rheumatoid arthritis and periodontitis.

Keywords

OVX mouse model; RANKL; calcium signal; eudebeiolide B; osteoporosis.

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