Euphorbia factor L1 inhibits osteoclastogenesis by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast

Seong Eun Hong, Jiae Lee, Dong Hyun Seo, Hye In Lee, Doo Ri Park, Gong Rak Lee, You Jin Jo, Narae Kim, Minjung Kwon, Hansem Shon, Eun Kyoung Seo, Han Sung Kim, Soo Young Lee, Woojin Jeong

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Abstract

Excessive bone resorption caused by increased osteoclast number or activity leads to a variety of bone diseases including osteoporosis, rheumatoid arthritis and periodontitis. Thus, the therapeutic strategy for these diseases has been focused primarily on the inhibition of osteoclast formation and function. This study shows that euphorbia factor L1 (EFL1), a diterpenoid isolated from Euphorbia lathyris, inhibited osteoclastogenesis and induced osteoclast apoptosis. EFL1 suppressed osteoclast formation and bone resorption at both initial and terminal differentiation stages. EFL1 inhibited receptor activator of NF-κB ligand (RANKL)-induced NFATc1 induction with attenuated NF-κB activation and c-Fos expression. EFL1 decreased the level of reactive oxygen species by scavenging them or activating Nrf2, and inhibited PGC-1β that regulates mitochondria biogenesis. In addition, EFL1 induced apoptosis in differentiated osteoclasts by increasing Fas ligand expression followed by caspase activation. Moreover, EFL1 inhibited inflammation-induced bone erosion and ovariectomy-induced bone loss in mice. These findings suggest that EFL1 inhibits osteoclast differentiation by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast, and may provide therapeutic potential for preventing or treating bone-related diseases caused by excessive osteoclast.

Original languageEnglish
Pages (from-to)191-199
Number of pages9
JournalFree Radical Biology and Medicine
Volume112
DOIs
Publication statusPublished - 2017 Nov

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

Hong, S. E., Lee, J., Seo, D. H., In Lee, H., Ri Park, D., Lee, G. R., Jo, Y. J., Kim, N., Kwon, M., Shon, H., Kyoung Seo, E., Kim, H. S., Young Lee, S., & Jeong, W. (2017). Euphorbia factor L1 inhibits osteoclastogenesis by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast. Free Radical Biology and Medicine, 112, 191-199. https://doi.org/10.1016/j.freeradbiomed.2017.07.030