Transient receptor potential vanilloid 4 (TRPV4) plays a pivotal role in chondrogenic mechanotransduction in ATDC5 cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670660
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Nagoya University
• Principal Investigator: Naoki Ishiguro 名古屋大学, 医学(系)研究科(研究院), 教授 (20212871)
• Co-Investigator(Kenkyū-buntansha): KITOH HIROSHI 名古屋大学, 医学系研究科, 准教授 (40291174) ; KOJIMA TOSHIHISA 名古屋大学, 医学部附属病院, 講師 (70378032) ; MISHIMA KENICHI 名古屋大学, 医学系研究科, 寄附講座助教 (40646519)
• Co-Investigator(Renkei-kenkyūsha): OHNO KINJI 名古屋大学, 医学系研究科, 教授 (80397455)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: TRPV4 / ATDC5 / SOX9

Outline of Final Research Achievements

The study aimed to determine the role of transient receptor potential vanilloid 4 (TRPV4) in the response to mechanical stress in chondrogenic cells. Sox9 and AGC mRNA levels were significantly higher in cells after mechanical stress loading compared to cells that were not stretched. Up-regulation of Sox9 mRNA induced by mechanical stress was attenuated by RR and TRPV4 siRNA. A pharmacological activator of TRPV4, 4α-phorbol 12, 13-didecanoate (4αPDD), increased chondrogenesis. The findings suggest that Ca2+ signaling activated by mechanical stress and regulated by TRPV4 promotes chondrogenesis in ATDC5 cells. This suggests that artificial activation of TRPV4 may serve as an intervention for treating osteoarthritis.

Free Research Field

整形外科