Macrophage Infiltration is a Causative Factor for Ligamentum Flavum Hypertrophy through the Activation of Collagen Production in Fibroblasts

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K15668
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kyushu University
• Principal Investigator: Okada Seiji 九州大学, 生体防御医学研究所, 教授 (30448435)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 黄色靭帯 / 腰部脊柱管狭窄症

Outline of Final Research Achievements

Ligamentum flavum (LF) hypertrophy causes lumbar spinal canal stenosis, leading to leg pain and disability in activities of daily living in elderly individuals. Although there have been previous studies on LF hypertrophy, its pathomechanisms have not fully elucidated. In this study, we demonstrated that infiltrating macrophages were a causative factor for LF hypertrophy. Induction of macrophages into the mouse LF by applying a micro-injury resulted in LF hypertrophy along with collagen accumulation and fibroblasts proliferation at the injured site, which were very similar to the characteristics observed in the severely hypertrophied LF of human. However, we found that macrophage depletion by injecting clodronate-containing liposomes counteracted LF hypertrophy even with micro-injury. These results suggested that macrophage infiltration was crucial for LF hypertrophy by stimulating collagen production in fibroblasts, providing better understanding the pathophysiology of LF hypertrophy.

Free Research Field

脊椎脊髄病学

Academic Significance and Societal Importance of the Research Achievements

我々の成果は、黄色靭帯肥厚の分子生物学的メカニズムにアプローチした初めての報告であり、同時に黄色靭帯肥厚研究における再現性のあるマウスモデルを確立したものである。現在、黄色靭帯肥厚による腰部脊柱管狭窄症や神経根圧迫による下肢症状に対しては、手術加療による黄色靭帯切除しかないが、将来的には１型コラーゲンの融解などで低侵襲に病態を改善できる可能性があり、本研究で確立した動物モデルが有効に活用されるものと考えている。