Identification of a novel compound that inhibits osteoclastogenesis by suppressing nucleoside transporters

Shun Katsuyama, Kumi Sugino, Yukiko Sasazawa, Yoshihiko Nakano, Harumi Aono, Keisuke Morishita, Makoto Kawatani, Kazuo Umezawa, Hiroyuki Osada, Siro Simizu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

We screened small-molecule compounds that inhibit osteoclast differentiation to find new anti-osteoporosis agents and found that a novel compound, SUKU-1, suppressed osteoclastogenesis. We also synthesized 38 derivatives of SUKU-1 and discovered that nine of them had inhibitory effects on osteoclastogenesis and that SUKU-33 was the most potent inhibitor. Next, we investigated the mechanisms by which SUKU-33 suppressed osteoclast differentiation. By measuring the uptake of [3H]-uridine in cells, we found that SUKU-33 suppressed both equilibrative nucleoside transporters and concentrative nucleoside transporters. These results suggest that SUKU-33 inhibits osteoclast differentiation by suppressing nucleoside transporters.

Original languageEnglish
Pages (from-to)1152-1162
Number of pages11
JournalFEBS Letters
Volume590
Issue number8
DOIs
Publication statusPublished - 2016 Apr 1

Fingerprint

Nucleoside Transport Proteins
Osteoclasts
Osteogenesis
Uridine
Osteoporosis
Derivatives
Molecules

Keywords

  • concentrative nucleoside transporter
  • equilibrative nucleoside transporter
  • osteoclast differentiation
  • osteoporosis

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

Identification of a novel compound that inhibits osteoclastogenesis by suppressing nucleoside transporters. / Katsuyama, Shun; Sugino, Kumi; Sasazawa, Yukiko; Nakano, Yoshihiko; Aono, Harumi; Morishita, Keisuke; Kawatani, Makoto; Umezawa, Kazuo; Osada, Hiroyuki; Simizu, Siro.

In: FEBS Letters, Vol. 590, No. 8, 01.04.2016, p. 1152-1162.

Research output: Contribution to journalArticle

Katsuyama, S, Sugino, K, Sasazawa, Y, Nakano, Y, Aono, H, Morishita, K, Kawatani, M, Umezawa, K, Osada, H & Simizu, S 2016, 'Identification of a novel compound that inhibits osteoclastogenesis by suppressing nucleoside transporters', FEBS Letters, vol. 590, no. 8, pp. 1152-1162. https://doi.org/10.1002/1873-3468.12146
Katsuyama S, Sugino K, Sasazawa Y, Nakano Y, Aono H, Morishita K et al. Identification of a novel compound that inhibits osteoclastogenesis by suppressing nucleoside transporters. FEBS Letters. 2016 Apr 1;590(8):1152-1162. https://doi.org/10.1002/1873-3468.12146
Katsuyama, Shun ; Sugino, Kumi ; Sasazawa, Yukiko ; Nakano, Yoshihiko ; Aono, Harumi ; Morishita, Keisuke ; Kawatani, Makoto ; Umezawa, Kazuo ; Osada, Hiroyuki ; Simizu, Siro. / Identification of a novel compound that inhibits osteoclastogenesis by suppressing nucleoside transporters. In: FEBS Letters. 2016 ; Vol. 590, No. 8. pp. 1152-1162.
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AU - Morishita, Keisuke

AU - Kawatani, Makoto

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