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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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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Osteoclasts
Osteogenesis
Oxidation-Reduction
Apoptosis
Bone
Bone Diseases
Bone Resorption
Chemical activation
Euphorbia
Osteitis
Mitochondria
Fas Ligand Protein
euphorbia factor L1
Diterpenes
Periodontitis
Scavenging
Ovariectomy
Caspases
Osteoporosis
Erosion

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

Hong, Seong Eun ; Lee, Jiae ; Seo, Dong Hyun ; In Lee, Hye ; Ri Park, Doo ; Lee, Gong Rak ; Jo, You Jin ; Kim, Narae ; Kwon, Minjung ; Shon, Hansem ; Kyoung Seo, Eun ; Kim, Han Sung ; Young Lee, Soo ; Jeong, Woojin. / Euphorbia factor L1 inhibits osteoclastogenesis by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast. In: Free Radical Biology and Medicine. 2017 ; Vol. 112. pp. 191-199.
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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.",
author = "Hong, {Seong Eun} and Jiae Lee and Seo, {Dong Hyun} and {In Lee}, Hye and {Ri Park}, Doo and Lee, {Gong Rak} and Jo, {You Jin} and Narae Kim and Minjung Kwon and Hansem Shon and {Kyoung Seo}, Eun and Kim, {Han Sung} and {Young Lee}, Soo and Woojin Jeong",
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Hong, SE, Lee, J, Seo, DH, In Lee, H, Ri Park, D, Lee, GR, Jo, YJ, Kim, N, Kwon, M, Shon, H, Kyoung Seo, E, Kim, HS, 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, vol. 112, pp. 191-199. https://doi.org/10.1016/j.freeradbiomed.2017.07.030

Euphorbia factor L1 inhibits osteoclastogenesis by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast. / Hong, Seong Eun; Lee, Jiae; Seo, Dong Hyun; In Lee, Hye; Ri Park, Doo; Lee, Gong Rak; Jo, You Jin; Kim, Narae; Kwon, Minjung; Shon, Hansem; Kyoung Seo, Eun; Kim, Han Sung; Young Lee, Soo; Jeong, Woojin.

In: Free Radical Biology and Medicine, Vol. 112, 11.2017, p. 191-199.

Research output: Contribution to journalArticle

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T1 - Euphorbia factor L1 inhibits osteoclastogenesis by regulating cellular redox status and induces Fas-mediated apoptosis in osteoclast

AU - Hong, Seong Eun

AU - Lee, Jiae

AU - Seo, Dong Hyun

AU - In Lee, Hye

AU - Ri Park, Doo

AU - Lee, Gong Rak

AU - Jo, You Jin

AU - Kim, Narae

AU - Kwon, Minjung

AU - Shon, Hansem

AU - Kyoung Seo, Eun

AU - Kim, Han Sung

AU - Young Lee, Soo

AU - Jeong, Woojin

PY - 2017/11

Y1 - 2017/11

N2 - 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.

AB - 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.

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