Regulation of osteoarthritic pain by M2 macrophages

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24037
• 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: Takano Shotaro 北里大学, 医学部, 助教 (10596505)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 神経ペプチド / M2マクロファージ / 疼痛

Outline of Final Research Achievements

We investigated role of peptide Lv in osteoarthritic pain. Bone marrow macrophages (BMM) BMM were stimulate with vehicle, LPS, or LPS + peptide Lv, and Tnfa expression and TNF-α productio. To examine the effect of peptide Lv deficiency on macrophages and synovitis, peptide Lv-deficient mice were generated using genome editing. LPS-induced Tnfa expression and TNF-α production were evaluated in BMM isolated from wildtype and peptide Lv-deficient mice. Additionally, Tnfa expression levels were compared between wildtype and peptide Lv-deficient mice with and without synovitis. Peptide Lv suppressed the LPS-mediated elevation in TNF-α. LPS stimulation significantly increased Tnfa expression and TNF-α production in BMM derived from peptide Lv-deficient mice compared to wildtype mice. Synovial TNF-α expression was elevated in peptide Lv-deficient compared to wildtype mice with synovitis. Peptide Lv may be a useful therapeutic target for synovitis.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

変形性関節症における疼痛は患者の生活の質、日常生活動作を著しく低下させるため、健康寿命の延伸には疼痛治療は極めて重要である。本研究成果は新たな疼痛治療標的を供給するものであり、新規治療薬の開発に繋がる可能性を秘めている。