Lumbar spinal stenosis (LSS) is a degenerative disease characterized by intermittent claudication and numbness in the lower extremities. These symptoms are caused by the compression of nerve tissue in the lumbar spinal canal. Ligamentum flavum (LF) hypertrophy and spinal epidural lipomatosis in the spinal canal are known to contribute to stenosis of the spinal canal: however, detailed mechanisms underlying LSS are still not fully understood. Here, we show that surgically harvested LFs from LSS patients exhibited significantly increased thickness when transthyretin (TTR), the protein responsible for amyloidosis, was deposited in LFs, compared to those without TTR deposition. Multiple regression analysis, which considered age and BMI, revealed a significant association between LF hypertrophy and TTR deposition in LFs. Moreover, TTR deposition in LF was also significantly correlated with epidural fat (EF) thickness based on multiple regression analyses. Mesenchymal cell differentiation into adipocytes was significantly stimulated by TTR in vitro. These results suggest that TTR deposition in LFs is significantly associated with increased LF hypertrophy and EF thickness, and that TTR promotes adipogenesis of mesenchymal cells. Therapeutic agents to prevent TTR deposition in tissues are currently available or under development, and targeting TTR could be a potential therapeutic approach to inhibit LSS development and progression.

腰椎管狭窄症（LSS）是一种以下肢间歇性跛行和麻木为特征的退行性疾病。这些症状是由于腰椎管内的神经组织受压而引起的。已知椎管内黄韧带 (LF) 肥大和脊髓硬膜外脂肪增多会导致椎管狭窄：然而，LSS 的详细机制仍不完全清楚。在这里，我们发现，与没有沉积 TTR 的 LF 相比，当导致淀粉样变性的蛋白质运甲状腺素蛋白 (TTR) 沉积在 LF 中时，手术采集的 LSS 患者的 LF 的厚度显着增加。多元回归分析考虑了年龄和 BMI，揭示了 LF 肥大与 LF 中 TTR 沉积之间存在显着关联。此外，根据多元回归分析，LF 中的 TTR 沉积也与硬膜外脂肪 (EF) 厚度显着相关。体外 TTR 显着刺激间充质细胞分化为脂肪细胞。这些结果表明，LF 中的 TTR 沉积与 LF 肥大和 EF 厚度增加显着相关，并且 TTR 促进间充质细胞的脂肪生成。目前已有或正在开发预防 TTR 在组织中沉积的治疗药物，而靶向 TTR 可能是抑制 LSS 发生和进展的潜在治疗方法。