Contribution of Mast cells in pathology of obese osteoarthritis patients

• Project/Area Number: 20K18073
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kitasato University
• Principal Investigator: Takano Shotaro 北里大学, 医学部, 助教 (10596505)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 変形性関節症 / 肥満 / 肥満細胞 / CD88 / IL-13 / bFGF / 炎症性サイトカイン / トリプターゼ

Outline of Research at the Start

OA患者から採取した滑膜組織を用いて①肥満細胞マーカーと疼痛、OA gradeとの関連性、②肥満細胞が産生する神経ペプチド、マトリックス分解酵素の探索、③肥満細胞とマクロファージ、線維芽細胞インターラクションの検討を行う。さらに、④ゲノム編集により肥満細胞欠失させたOAモデルマウスを作製し、検討を行う。

Outline of Final Research Achievements

The mechanisms governing evidence that obesity is a risk factor for osteoarthritis (OA) are not well understood. This study investigated the expression of the β-tryptase encoding gene, TPSB2, in the SM of obese patients with knee OA and β-tryptase-mediated regulation of IL-1β in synovial cells.
A total of 216 patients radiographically diagnosed with knee OA were grouped according to the World Health Organization’s body mass index (BMI) classifications: normal weight (NW), overweight (OW) and obese (OB). There was significantly elevated TPSB2 expression in the OW and OB groups compared to the NW group. The MC-rich fraction had significantly higher levels of TPSB2, CD117 and CD203c than the MC-poor fraction. Recombinant human β-tryptase stimulated IL1B expression in both the synovial fibroblast and macrophage fractions. Obese patients with knee OA showed elevated TPSB2 expression in the SM. Tryptase may play a role in synovial inflammation in obese patients with OA.

Academic Significance and Societal Importance of the Research Achievements

肥満変形性関節症患者の病態に肥満細胞およびその産生因子が関与することを示した。本研究成果は、２４００万人を超える変形性関節症患者の新規治療法開発に貢献できると考えられる。

Research Products

• [Journal Article] Possible Regulation of bFGF Expression by Mast Cells in Osteoarthritis Patients with Obesity: A Cross-Sectional Study (2021)
  • Author(s): Takata K, Uchida K, Takano S, Mukai M, Inoue G, Sekiguchi H, Aikawa J, Miyagi M, Iwase D, Takaso M
  • Journal Title: Diabetes Metab Syndr Obes Volume: 14 Pages: 3291-3297
  • DOI: 10.2147/dmso.s319537
  • Peer Reviewed
• [Journal Article] Increase in Tryptase and Its Role in the Synovial Membrane of Overweight and Obese Patients with Osteoarthritis of the Knee (2020)
  • Author(s): Takata K, Uchida K, Mukai M, Takano S, Aikawa J, Iwase D, Sekiguchi H, Miyagi M, Inoue G, Takaso M
  • Journal Title: Diabetes Metab Syndr Obes Volume: 13 Pages: 1491-1497
  • DOI: 10.2147/dmso.s253147
  • Peer Reviewed / Open Access
• [Presentation] 変形性膝関節症の滑膜組織におけるAdrenomedullinと肥満細胞との関連性の検討 (2020)
  • Author(s): 高野昇太郎、内田健太郎、高田研、迎 学、相川 淳、岩瀬大、井上玄、高相晶士
  • Organizer: 第35回日本整形外科学会基礎学術集会