Relationship between infrapatellar fat pad derived neuropeptides and osoteoarthritic pain

• Project/Area Number: 19K09606
• 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: Kitasato University
• Principal Investigator: Aikawa Jun 北里大学, 医学部, 講師 (90317008)
• Co-Investigator(Kenkyū-buntansha): 内田 健太郎 北里大学, 医学部, 講師 (50547578) ; 大久保 直 北里大学, 医学部, 准教授 (10450719)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 膝蓋下脂肪体 / 神経ペプチド / 疼痛 / 変形性関節症

Outline of Research at the Start

膝蓋下脂肪体由来神経ペプチドを介した変形性膝関節症（OA）における新規疼痛発生機序の解明を目指す。本研究では、OA患者より採取した膝蓋下脂肪体組織とゲノム編集により神経ペプチド制御因子をノックアウトした新規OAマウスを用いることで、膝蓋下脂肪体由来神経ペプチドを介した疼痛発生機序の解明を行う。

Outline of Final Research Achievements

The infrapatellar fat pad (IPFP) has been implicated as a possible source of osteoarthritis (OA) development and knee pain due to the production of inflammatory mediators. Neuropeptides are localized to joint tissues and has recently been implicated in the development of knee OA and OA pain. To date, however, the expression levels of neuropeptides in the IPFP of human knee OA patients have not been examined.We analyzed IPFP obtained from knee OA patients and found that the expression levels of apelin in the IPFP were positively correlated with pain score at rest. The expression levels of Peptide Lv in the IPFP were negatively correlated with pain score at rest. Peptide Lv deficient mice exhibited inflammatory phenotype. Apelin and Peptide Lv in IPFP may be a therapeutic target for OA pain

Academic Significance and Societal Importance of the Research Achievements

本邦では疼痛を有する変形性膝関節症患者が800万人存在することが明らかになっている。本研究で同定した疼痛関連ペプチドは疼痛治療標的となる可能性を秘めており、健康寿命の延伸に貢献し得る。

Research Products

• [Journal Article] Increase in CD5L expression in the synovial membrane of knee osteoarthritis patients with obesity (2021)
  • Author(s): Shoji S, Uchida K, Inoue G, Takata K, Mukai M, Aikawa J, Iwase D, Takano S, Sekiguchi H, Takaso M
  • Journal Title: Cent Eur J Immunol Volume: 46 Issue: 2 Pages: 231-235
  • DOI: 10.5114/ceji.2021.108180
  • Peer Reviewed / Open Access
• [Journal Article] Increase in CD5L expression in the synovial membrane of knee osteoarthritis patients with obesity (2020)
  • Author(s): Shoji S, Uchida K, Inoue G, Takata K, Mukai M, Aikawa J, Iwase D, Takano S, Sekiguchi H, Takaso M
  • Journal Title: Cent Eur J Immunol Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] Osteoarthritis patients with high haemoglobin A1c have increased Toll-like receptor 4 and matrix metalloprotease-13 expression in the synovium. (2019)
  • Author(s): Murata K, Uchida K, Takano S, Shoji S, Iwase D, Aikawa J, Yokozeki Y, Sekiguchi H, Takaso M.
  • Journal Title: Diabetes Metab Syndr Obes Volume: 12 Pages: 1151-1159
  • DOI: 10.2147/dmso.s209677
  • Peer Reviewed / Open Access
• [Presentation] 肥満を伴う変形性膝関節症患者の滑膜組織ではCD5Lが増加する (2020)
  • Author(s): 庄司真太郎、内田健太郎、井上玄、高田研、迎学、相川淳、岩瀬大、高野昇太郎、関口裕之、髙相晶士
  • Organizer: 第35回日本整形外科学会基礎学術集会
• [Presentation] HbA1c高値の変形性膝関節症患者の滑膜組織ではToll-like receptor-4とMMP-13が亢進している． (2019)
  • Author(s): 村田幸佑、内田健太郎、高野昇太郎、相川淳、岩瀬大、井上玄、関口裕之、大貫裕子、高相晶士
  • Organizer: 第34回日本整形外科学会基礎学術集会