論文

査読有り
2009年8月

Direct Inhibitory and Indirect Stimulatory Effects of RAGE Ligand S100 on sRANKL-Induced Osteoclastogenesis

JOURNAL OF CELLULAR BIOCHEMISTRY
  • Tomohiko Yoshida
  • ,
  • Ayanna Flegler
  • ,
  • Andrew Kozlov
  • ,
  • Paula H. Stern

107
5
開始ページ
917
終了ページ
925
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/jcb.22192
出版者・発行元
WILEY-LISS

Diabetes results in increased fracture risk, and advance glycation endproducts (AGEs) have been implicated in this pathophysiology. S100 proteins are ligands for the receptor of AGEs (RAGE). An intracellular role of the S100 family member S100A4 (Mts1) to suppress mineralization has been described in pre-osteoblastic MC3T3-E1 cells. However, S100 proteins could have additional effects on bone. The goal of the current study was to determine effects of increased extracellular S100 on osteoclastogenesis. We first determined the direct effects of S100 on pre-osteoclast proliferation and osteoclastic differentiation. RANKL-treated RAW 264.7 cell proliferation and TRAP activity were significantly inhibited by S100, and the number and size of TRAP-positive multinucleated cells were decreased. We then determined whether S100 could affect osteoclastogenesis by an indirect process by examining effects of conditioned media from S100-treated MC3T3-E1 cells on osteoclastogenesis. In contrast to the direct inhibitory effect of S100, the conditioned media promoted RAW 264.7 cell proliferation and TRAP activity, with a trend toward increased TRAP-positive multinucleated cells. S100 treatment of the MC3T3-E1 cells for 14 days did not significantly affect alkaline phosphatase, M-CSF, or OPG gene expression. RANKL was undetectable in both untreated and treated cells. The treatment slightly decreased MC3T3-E1 cell proliferation. Interestingly, S100 treatment increased expression of RAGE by the MC3T3-E1 cells. This suggested the possibility that S100 could increase soluble RAGE, which acts as a decoy receptor for S100. This decrease in availability of S100, an inhibitor of pre-osteoclast proliferation, could contribute to osteoclastogenesis, ultimately resulting in increased bone resorption. J. Cell. Biochem. 107: 917-925, 2009. (C) 2009 Wiley-Liss, Inc.

Web of Science ® 被引用回数 : 17

リンク情報
DOI
https://doi.org/10.1002/jcb.22192
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19415676
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000268542500010&DestApp=WOS_CPL

エクスポート
BibTeX RIS