Analysis on the pharmacological mechanism of W9 peptide and development for the novel drug based on the strong potential for chondrocyte differentiation

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H02918
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Ikebuchi Yuki 東京大学, 医学部附属病院, 助教 (20645725)
• Co-Investigator(Kenkyū-buntansha): 本間 雅 東京大学, 医学部附属病院, 講師 (60401072)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 軟骨代謝 / Wペプチド / 細胞内シグナル / 抗体創薬

Outline of Final Research Achievements

The purpose of this study is to elucidate the pharmacological target of W9 peptide, which shows the potential of chondrogenesis. At first, we searched binding target of W9 peptide using avidin-streptavidin pulldown method, and a couple of cell surface proteins were identified. Therefore, we performed knockdown and knockout experiment in ATDC5, a chondrocyte like cell derived from mice, to examine the involvement of these proteins. Furthermore, downstream signaling pathways in W9-stimulated ATDC5 cells were confirmed by phosphorylated proteomics analysis. Based on these analyses, we designed bispecific antibodies to crosslink W9 target proteins, which may mimic biotin-labelled W9 peptide, and evaluate pharmacological effects.

Free Research Field

骨・軟骨代謝

Academic Significance and Societal Importance of the Research Achievements

変形性関節症などの軟骨関連疾患は、健康寿命を縮める主な要因の一つであり、超高齢化社会へと進展している現在では克服すべき課題となっている。ビオチン修飾を施したW9ペプチドは、軟骨細胞分化に関わる他の分子と比較しても強い活性を有しており、これを選択的に入力できる抗体医薬の開発に成功すれば、臨床的に非常に大きな意義を持つ。また、得られた抗体分子の構造最適化に関する知見は、他の疾患治療薬の開発にも活かせることが期待され、今後の研究活動の基盤になるものと考えている。