Spotlights

[Research News] Fine-Tuning Osteoclast Development: A Targeted Approach to Bone Disease

Professor Kiyotaka Nishikawa's research team has developed a tetravalent peptide that modulates a key bone resorption pathway, paving the way for effective treatments with fewer side effects.

Bone-destructive diseases often arise from overactive osteoclasts, driven by the RANK-TRAF6 signaling pathway. However, treatments targeting this pathway also affect other biological processes. Now, researchers have developed a new tetravalent peptide, CR4-WHD-tet, that fine-tunes this pathway. CR4-WHD-tet selectively inhibits signals important for late-stage osteoclast maturation without disrupting the pathway’s other essential functions. This innovative approach could lead to targeted therapies with reduced side effects for osteoporosis and similar diseases.

Reference

Masataka Anzai, Miho Watanabe-Takahashi, Hiroshi Kawabata, Yuri Masuda, Aoi Ikegami, Yuta Okuda, Tsuyoshi Waku, Hiroaki Sakurai, Keizo Nishikawa, Jun-ichiro Inoue, Kiyotaka Nishikawa, Clustered peptide regulating the multivalent interaction between RANK and TRAF6 inhibits osteoclastogenesis by fine-tuning signals, Communications Biology 8, Article number: 643 (2025) 
DOI :10.1038/s42003-025-08047-2

For more details, please see the website of Organization for Research Initiatives and Development, Doshisha University. 

https://research.doshisha.ac.jp/news/news-detail-74/

This achievement has also been featured in the “EurekAlert!.”

https://www.eurekalert.org/news-releases/1084690

Image title: Inhibiting a specific downstream effect in the RANK-TRAF6 signaling pathway
Image caption: Rather than completely blocking all downstream signals, the peptide developed in this study focuses on inhibiting the activation of p38-MAPK. This is enough to downregulate the development of mature osteoclasts without affecting unrelated biological processes as a side effect.
Image credit: Professor Kiyotaka Nishikawa from Doshisha University, Japan
License type: Original content
Usage restrictions: Cannot be reused without permission.