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Transthyretin amyloid deposition in ligamentum flavum (LF) is significantly correlated with LF and epidural fat hypertrophy in patients with lumbar spinal stenosis.


ABSTRACT: 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.

SUBMITTER: Maeda K 

PROVIDER: S-EPMC10654520 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Transthyretin amyloid deposition in ligamentum flavum (LF) is significantly correlated with LF and epidural fat hypertrophy in patients with lumbar spinal stenosis.

Maeda Kazuya K   Sugimoto Kazuki K   Tasaki Masayoshi M   Taniwaki Takuya T   Arima Takahiro T   Shibata Yuto Y   Tateyama Makoto M   Karasugi Tatsuki T   Sueyoshi Takanao T   Masuda Tetsuro T   Uehara Yusuke Y   Tokunaga Takuya T   Hisanaga Satoshi S   Yugami Masaki M   Yonemitsu Ryuji R   Ideo Katsumasa K   Matsushita Kozo K   Fukuma Yuko Y   Uragami Masaru M   Kawakami Junki J   Yoshimura Naoto N   Takata Kosei K   Shimada Masaki M   Tanimura Shuntaro S   Matsunaga Hideto H   Kai Yuki Y   Takata Shu S   Kubo Ryuta R   Tajiri Rui R   Homma Fuka F   Tian Xiao X   Ueda Mitsuharu M   Nakamura Takayuki T   Miyamoto Takeshi T  

Scientific reports 20231116 1


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 p  ...[more]

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