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

Autor: Narae Kim, Dong Hyun Seo, Hansem Shon, Woojin Jeong, Hye In Lee, Seong Eun Hong, Hansung Kim, Jiae Lee, You Jin Jo, Minjung Kwon, Doo Ri Park, Gong Rak Lee, Soo Young Lee, Eun Kyoung Seo
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Osteoclasts
Apoptosis
Biochemistry
Fas ligand
Mice
0302 clinical medicine
Osteogenesis
Phenylpropionates
NF-kappa B
Cell Differentiation
Fas receptor
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Cell biology
medicine.anatomical_structure
RANKL
Caspases
030220 oncology & carcinogenesis
Female
Diterpenes
Signal transduction
Proto-Oncogene Proteins c-fos
Signal Transduction
musculoskeletal diseases
medicine.medical_specialty
Fas Ligand Protein
NF-E2-Related Factor 2
Primary Cell Culture
Biology
Bone resorption
03 medical and health sciences
Osteoclast
Physiology (medical)
Internal medicine
medicine
Animals
fas Receptor
Bone Resorption
NFATC Transcription Factors
Macrophages
RANK Ligand
Mice
Inbred C57BL
030104 developmental biology
Endocrinology
Gene Expression Regulation
biology.protein
Reactive Oxygen Species
Zdroj: Free Radical Biology and Medicine. 112:191-199
ISSN: 0891-5849
DOI: 10.1016/j.freeradbiomed.2017.07.030
Popis: 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.
Databáze: OpenAIRE
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