Regulation of NGF by macrophage in intervertebral discs

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22984
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0906:Surgery related to the biological and sensory functions and related fields
• Research Institution: Kitasato University
• Principal Investigator: Nakawaki Mitsufumi 北里大学, 医学部, 助教 (00623175)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 神経成長因子 / 椎間板性腰痛 / TGF-β

Outline of Final Research Achievements

We studied NGF regulation in a mouse model of IVD injury. We examined mRNA levels of Tnfa, Tgfb, and Ngf in IVDs from control and IVD-injured mice.We used magnetic cell separation to isolate macrophage-rich and IVD cell-richfractions from injured IVDs. We also examined Ngf expression in injured IVDs from C57BL/6 J and Tnfa-knockout (KO) mice. To study the effect of TGF-β on Ngf expression, C57/BL6J mice were given an intraperitoneal injection of TGF-β inhibitor, SB431542 one and two days before harvesting IVDs. Tnfa, Tgfb, and Ngf expression was significantly increased in injured IVDs. Tnfa was predominantly expressed in the CD11b ( +) fraction, and Tgfb in the CD11b (-) fraction. Ngf expression was comparable between CD11b ( +) and CD11b (-) fractions, and between wild-type and Tnfa-KO mice. SB431542 suppressed TGF-β-mediated Ngf expression and NGF production in vitro. Further, SB431542 significantly reduced Ngf expression in IVDs.TGF-β may regulate NGF expression in vivo.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

腰痛の生涯罹患率は85％と報告され、超高齢者社会を迎えた我が国における腰痛患者は
2,800万人にものぼる。腰痛による経済損失は年間7,000億円と推定されている。本研究で異化はNGFおよびNGF制御因子を標的とした腰痛治療の開発に役立つものと考えられる。