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| Titel: |
Phenethyl isothiocyanate suppresses receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis by blocking activation of ERK1/2 and p38 MAPK in RAW264.7 macrophages |
| Auteur: |
Murakami, Akira Song, Meiyu Ohigashi, Hajime |
| Verschenen in: |
BioFactors |
| Paginering: | Jaargang 30 (2008) nr. 1 pagina's 1-11 |
| Jaar: |
2008-01-07 |
| Inhoud: |
Osteoclastogenesis is induced by differentiation of hemopoietic cells of monocyte-macrophage lineage into bone-resorbing osteoclasts. The process is initiated by receptor activator of NF-kappaB ligand (RANKL) and resultant activation of mitogen-activated protein kinases (MAPK), including extracellular signal-regulated kinase (ERK)1/2, as well as the NFκB pathway. Phenethyl isothiocyanate (PEITC), a phytochemical present in various cruciferous plants, has been shown to disrupt those signaling pathways in several cell types. In this study, we examined the efficacy of PEITC for suppressing RANKL-induced osteoclastogenesis in RAW264.7 murine macrophages and addressed the underlying molecular mechanisms. PEITC (2–10 μM) suppressed osteoclastogenesis in a concentration dependent manner, as detected by tartarate-resistant acid phosphatase (TRAP) activity and microscopic observations. RANKL-up-regulated extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) activities were attenuated by PEITC, whereas c-Jun N-terminal kinase (JNK1/2) activation was increased. PEITC also abrogated the RANKL-induced degradation of IκB-α, a suppressive partner of nuclear factor kappaB (NFκB), thereby inhibiting transcription activity, as detected by a reporter assay. In addition, PEITC reduced the level of NFκB-dependent mRNA expression of nuclear factor of activated T cell (NFAT)c1, a master regulator of osteoclastogenesis. Our results indicate that PEITC is a promising agent for treatment of osteoclastogenesis with a reasonable action mechanism. |
| Uitgever: |
IOS Press |
| Bronbestand: |
Elektronische Wetenschappelijke Tijdschriften |
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