Ganomycin I from Ganoderma lucidum attenuates RANKL-mediated osteoclastogenesis by inhibiting MAPKs and NFATc1

  • Phytomedicine. 2019 Mar 1;55:1-8. doi: 10.1016/j.phymed.2018.10.029.
Phuong Thao Tran  1 ,  Nguyen Tien Dat  2 ,  Nguyen Hai Dang  3 ,  Pham Van Cuong  3 ,  Suhyun Lee  1 ,  Cheol Hwangbo  4 ,  Chau Van Minh  3 ,  Jeong-Hyung Lee  5
Affiliations
  • 1. Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 24341, Republic of Korea.
  • 2. Center for Research and Technology Transfer, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
  • 3. Advanced Center for Bio-Organic Chemistry, Institute of Marine Biochemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
  • 4. Division of Applied Life Science (BK21 Plus), PMBBRC, Division of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea.
  • 5. Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-Do 24341, Republic of Korea. Electronic address: [email protected].
PMID: 30668419 DOI: 10.1016/j.phymed.2018.10.029
Abstract

Background: Many bone-related diseases such as osteoporosis and rheumatoid arthritis are commonly associated with excessive activity of the osteoclast. Ganomycin I (GMI), a meroterpenoid isolated from Vietnamese mushroom Ganoderma lucidum, possesses a variety of beneficial effects on human health. However, its impact and underlying mechanism on osteoclastogenesis remain unclear. In the present study, we investigated the effect of GMI on RANKL-induced osteoclast formation in mouse BMMs and RAW264.7 cells.

Methods: BMMs or RAW264.7 cells were treated with GMI followed by an evaluation of cell viability, RANKL-induced osteoclast differentiation, actin-ring formation, and resorption pits activity. Effects of GMI on RANKL-induced phosphorylation of MAPKs as well as the expression levels of NFATc1 and c-Fos were evaluated by Western blot analysis. Expression levels of osteoclast marker genes were evaluated by Western blot analysis and reverse transcription-qPCR.

Results: GMI significantly inhibited RANKL-induced osteoclast differentiation by decreasing the number of osteoclasts, osteoclast actin-ring formation, and bone resorption in a dose-dependent manner without affecting cell viability. At molecular level, GMI inhibited the RANKL-induced phosphorylation of ERK, JNK, and p38 MAPKs, as well as the expression levels of c-Fos and NFATc1, which are known to be crucial transcription factors for osteoclast formation. In addition, GMI decreased expression levels of osteoclastogenesis specific marker genes including c-Src, CtsK, TRAP, MMP-9, OSCAR, and DC-STAMP in RANKL-stimulated BMMs.

Conclusion: Our findings suggest that GMI can attenuate osteoclast formation by suppressing RANKL-mediated MAPKs and NFATc1 signaling pathways and the anti-osteoclastogenic activity of GMI may extend our understanding of molecular mechanisms underlying biological activities and pharmacological use of G. lucidum as a traditional anti-osteoporotic medicine.

Keywords
Ganoderma lucidum; Ganomycin I; MAPKs; NFATc1; Osteoclastogenesis; RANKL.
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