Analysis of new therapeutic target molecules for osteoporosis based on the chromatin information

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19728
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Surgery related to the biological and sensory functions and related fields
• Research Institution: Ehime University
• Principal Investigator: Imai Yuuki 愛媛大学, プロテオサイエンスセンター, 教授 (10423873)
• Research Collaborator: Yanagihara Yuta ; Iimura Tadahiro ; Saeki Noritaka ; Lee Jiwon
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 破骨細胞 / Zscan10 / 転写因子 / RNA-seq

Outline of Final Research Achievements

Zinc finger and SCAN domain containing 10 (Zscan10) was identified as a novel transcription factor that is involved in osteoclast differentiation in our previous report. However, the biological functions of Zscan10 are not fully understood. First, Zscan10 KO RAW264 (KO) cells were established by genome editing using CRISPR/Cas9 and single cell sorting. Zscan10 might regulate transcription of the genes that negatively control osteoclastogenesis. To understand gene expression profiles controlled by Zscan10, RNA-seq was performed and stringent analyses identified the haptoglobin gene (Hp) as a possible target of Zscan10. rHp treatment suppressed TRAP activity of KO cells without affecting cell viability. Furthermore, it has been reported that Hp KO mice exhibit decreased bone mass and increased osteoclast number. Taken together, this study suggests that Zscan10 negatively regulates osteoclast differentiation through transcription of Hp.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

新規破骨細胞転写因子Zscan10の同定から、統合的ゲノムワイド解析により明らかとなったハプトグロビン（Hp）が骨代謝制御の標的分子になりうることが明らかとなった。これまでにHp KOマウスでは骨量の減少及び破骨細胞数の増加を呈し、Hpが破骨細胞分化の抑制に関与すること、Hpが低値を示す溶血性貧血の患者では、骨量の減少を引き起こすことが報告されている。以上のような報告から、生体においてもHpが骨代謝に対し保護的作用を示すことが示唆された。