The elucidation of osteoarthritis pathogenesis based on the osteogenic culture experiment of induced pluripotent cells with the modification of oxygen tension

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09508
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Nara Medical University
• Principal Investigator: Inagaki Yusuke 奈良県立医科大学, 医学部, 准教授 (60707529)
• Co-Investigator(Kenkyū-buntansha): 岡村 建祐 奈良県立医科大学, 医学部附属病院, 研究員 (60812691)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 変形性膝関節症 / ヒト人工多能性幹細胞 / 低酸素

Outline of Final Research Achievements

Knee osteoarthritis (KOA) is a very important welfare and health issue, but the details of its pathogenesis at the molecular level have not yet been clarified. In this study, we used human induced pluripotent stem cells (iPSCs) to analyze the gene expression levels during changes in the oxygen concentration in culture to elucidate the pathogenesis of KOA and to contribute to the development of new therapeutic drugs for KOA in the future.
The results of this study showed that osteogenic differentiation of human iPS cells was demonstrated even under an oxygen concentration of 7% (hypoxia) and even when the oxygen concentration was changed during culture. Furthermore, it was suggested that osteogenic differentiation progressed by increasing the oxygen concentration during osteoinductive culture. These results suggest that changes in oxygen concentration in the microenvironment may contribute to KOA progression.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

変形性膝関節症(KOA)は膝関節への力学的ストレスを中心とした多因子性疾患であり、疼痛や可動域制限により活動性が低下し、Quality of Life (QOL) の悪化要因とされる。我が国では有症状者は780万人、単純X線写真で異常所見のある者は2530万人と高い有病率が推定されており(Yoshimura et al. J Bone Miner Metab 2009)、急速な高齢化により、今後ますますの患者数増加また、KOAは転倒リスクや大腿骨近部骨折のリスクとなり、社会的にもKOAの治療は大変重要な課題である。