Functional analysis of osteoclastogenesis inhibitor

2013 Fiscal Year Final Research Report

• Project/Area Number: 24810025
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Chemical biology
• Research Institution: Keio University
• Principal Investigator: SASAZAWA Yukiko 慶應義塾大学, 理工学部, 助教 (20594922)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Keywords: ケミカルバイオロジー / 破骨細胞 / 骨粗鬆症

Research Abstract

Bone homeostasis is maintained by both osteoclasts and osteoblasts. Osteoporosis is one of the bone diseases caused by collapse of bone homeostasis. Inhibitors of osteoclast differentiation are expected as new therapeutic agents for osteoporosis. We have found that TPh A inhibits osteoclast differentiation from bone marrow macrophages. We investigated the effects on RANKL-induced osteoclast differentiation of 50 TPh A derivatives in order to obtain a compound that inhibits osteoclastogenesis at a lower concentration than TPh A. We found that SUK-39 is the most potent osteoclastogenesis inhibitor. Moreover, RT-PCR analysis showed that SUK-39 suppressed RANKL-induced DC-STAMP and its transcription factor, c-fos mRNA level. These results indicated that SUK-39 inhibited osteoclast fusion by inhibiting expression of c-fos and subsequent DC-STAMP mRNA expression. SUK-39 would be a bioprobe for understanding the mechanisms of osteoclast fusion.

Research Products

• [Journal Article] Involvement of conserved tryptophan residues for secretion of TIMP-2 (2014)
  • Author(s): Ukaji, T., Sasazawa, Y., Umezawa, K. & Simizu, S.
  • Journal Title: Oncology Letters Volume: 7 Pages: 631-634
  • Peer Reviewed
• [Journal Article] Determination of topological structure of ARL6ip1 in cells : Identification of the essential binding region of ARL6ip1 for conophylline (2013)
  • Author(s): Kuroda, M., Funasaki, S., Saitoh, T., Sasazawa, Y., Nishiyama, S., Umezawa, K. & Simizu, S.
  • Journal Title: FEBS Letters Volume: 587 Pages: 3656–3660
  • Peer Reviewed
• [Presentation] Neuroprotective effect of conophylline in cellular model of Parkinson's disease (2013)
  • Author(s): ○Sasazawa, Y., Umezawa, K. & Simizu, S
  • Organizer: International Symposium on Mitochondria 2013
  • Place of Presentation: Tokyo
  • Year and Date: 20131100
• [Presentation] Antitumor activity of xanthohumol, an valosin-containing inhibitor of protein (2013)
  • Author(s): ○Shikata, Y., Kanagaki, S., Sasazawa, Y., Tashiro, E., Yoshimaru, T., Komatsu, M., Katagiri, T., Imoto, M.
  • Organizer: AACR-NCI-EORTC International conference MOLECULAR TARGETS AND CANCER THERAPEUTICS
  • Place of Presentation: Boston
  • Year and Date: 20131000
• [Presentation] Functional Analysis of Small Molecules Regulating Autophagy (2013)
  • Author(s): ○Sasazawa, Y.
  • Organizer: International Mini Symposium on Chemical Biology of Natural Products : Target ID and Regulation of Bioactivity
  • Place of Presentation: Yokohama
  • Year and Date: 20130300
• [Presentation] コノフィリンによる神経保護効果の解析 (2013)
  • Author(s): ○笹澤有紀子、梅澤一夫、清水史郎
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2013-12-04
• [Presentation] TPh A誘導体の破骨細胞分化に及ぼす影響と構造活性相関解析 (2013)
  • Author(s): ○森下佳典、笹澤有紀子、杉野公美、川谷誠、長田裕之、清水史郎
  • Organizer: 日本農芸化学会関東支部会2013年度大会
  • Place of Presentation: 横浜
  • Year and Date: 2013-11-22
• [Presentation] Conophyllineによるオートファジー誘導 (2013)
  • Author(s): ○笹澤有紀子、梅澤一夫、清水史郎
  • Organizer: 日本ケミカルバイオロジー学会第8回年会
  • Place of Presentation: 東京
  • Year and Date: 2013-06-21
• [Presentation] Conophylline標的タンパク質ARL6ip1の小胞体におけるトポロジー解析 (2013)
  • Author(s): ○黒田将広、宇梶珠未、笹澤有紀子、清水史郎
  • Organizer: 日本ケミカルバイオロジー学会第8回年会
  • Place of Presentation: 東京
  • Year and Date: 2013-06-20
• [Presentation] キサントフモールのオートファジー制御機構解析 (2012)
  • Author(s): ○笹澤有紀子、金墻周平、田代悦、野川俊彦、室井誠、近藤恭光、長田裕之、井本正哉
  • Organizer: 文部科学省科学研究費補助金「新学術領域研究」第4回「細胞内ロジスティクス」班会議
  • Place of Presentation: 仙台
  • Year and Date: 2012-06-13