RRC ID 43679
著者 Yamada K, Noguchi C, Kamitori K, Dong Y, Hirata Y, Hossain MA, Tsukamoto I, Tokuda M, Yamaguchi F.
タイトル Rare sugar D-allose strongly induces thioredoxin-interacting protein and inhibits osteoclast differentiation in Raw264 cells.
ジャーナル Nutr Res
Abstract Oxidative stress modulates the osteoclast differentiation via redox systems, and thioredoxin 1 (Trx) promotes the osteoclast formation by regulating the activity of transcription factors. The function of Trx is known to be regulated by its binding partner, thioredoxin-interacting protein (TXNIP). We previously reported that the expression of TXNIP gene is strongly induced by a rare sugar D-allose. In this study, we tested the hypothesis that D-allose could inhibit the osteoclast differentiation by regulating the Trx function. We used a murine Raw264 cell line that differentiates to the osteoclast by the receptor activator of nuclear factor-κB ligand (RANKL) treatment. The effect of sugars was evaluated by tartrate-resistant acid phosphatase staining. The expression and localization of TXNIP and Trx protein were examined by Western blotting and immunohistochemisty. The activity of the nuclear factor-κB, nuclear factor of activated T cells, and activator protein 1 transcription factors was measured by the luciferase reporter assay. The addition of D-allose (25 mmol/L) inhibited the osteoclast differentiation down to 9.53% ± 1.27% of a receptor activator of nuclear factor-κB ligand-only treatment. During the osteoclast differentiation, a significant increase of TNXIP was observed by D-allose treatment. The immunohistochemical analysis showed that both Trx and TXNIP existed in the nucleus in preosteoclasts and osteoclasts. Overexpression of TXNIP by plasmid transfection also inhibited the osteoclast formation, indicating the functional importance of TXNIP for the osteoclast differentiation. Transcriptional activity of the activator protein 1, nuclear factor-κB, and nuclear factor of activated T cells, known to be modulated by Trx, were inhibited by D-allose. In conclusion, our data indicate that D-allose is a strong inhibitor of the osteoclast differentiation, and this effect could be caused by TXNIP induction and a resulting inhibition of the Trx function.
巻・号 32(2)
ページ 116-23
公開日 2012-2-1
DOI 10.1016/j.nutres.2011.12.010
PII S0271-5317(11)00274-0
PMID 22348460
MeSH Animals Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Differentiation / drug effects* Cell Line Cell Nucleus Gene Expression Regulation / drug effects* Glucose / pharmacology* Mice Osteoclasts / drug effects* Osteoclasts / physiology Oxidative Stress / physiology Plasmids RANK Ligand / metabolism RANK Ligand / pharmacology Staining and Labeling Thioredoxins / genetics Thioredoxins / metabolism* Transcription Factors / metabolism Transcription, Genetic / drug effects* Transfection
IF 2.767
引用数 13
WOS 分野 NUTRITION & DIETETICS
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)