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Regulation of RANK expression mediated by L‐ascorbic acid in RAW264.7 cells:involvement of cNOS, NF‐kB and Ikaros
Author(s) -
Joo Haemi,
Son Eunwha,
Rhee DongKwon,
Pyo Suhkneung
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1100.2
Subject(s) - ascorbic acid , chemistry , activator (genetics) , osteoclast , transcription factor , microbiology and biotechnology , nf κb , regulator , cellular differentiation , rank ligand , receptor , rankl , biochemistry , biology , gene , signal transduction , food science
L‐ascorbic acid (AsA) has been known to induce osteoclastic differentiation through osteoclast differentiation factor in some osteogenic cells. However, the precise mechanism of AsA in osteoclastogenesis is not completely understood. This study investigated the effect of AsA on the expression of receptor activator of nuclear factor‐kappa B (RANK) which is indispensable for osteoclast differentiation. Our data showed that AsA treatment up‐regulated the expression of RANK mRNA and protein in RAW 264.7 cells, which was inhibited by DPI, cNOS inhibitor. AsA also induced the expression of cNOS protein, indicating that cNOS is involved in AsA‐induced RANK expression. The level of RANK expression was decreased in Ikaros dominant negative isoform‐overexpressed RAW 264.7 cells compared with that of control cells. In addition, AsA dose‐dependently increased the DNA binding affinity of the Ikaros transcription factor, suggesting that Ikaros acts as a positive regulator on RANK expression. DPI also inhibited the nuclear expression of NF‐kB p65 induced by AsA. Furthermore, DPI significantly decreased the DNA binding activity of NF‐kB induced by AsA, implicating that cNOS is clearly related to NF‐kB activity. Overall, the present data demonstrate that AsA might stimulate osteoclastic differentiation by enhancing RANK expression and this process might be related to cNOS, NF‐kB and ikaros activation.