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Although several causes of ligamentum flavum (LF) hypertrophy have been identified, the pathomechanisms underlying LF hypertrophy are not fully understood. Because collagen fibers are essential for the maintenance of LF tissues, characterization of the collagen composition of hypertrophied LF may help to elucidate the pathology of lumbar spinal canal stenosis (LCS). This study aimed to determine the association between the collagen composition and LF hypertrophy. LF tissues were collected from 23 patients who underwent spinal decompression surgery for lumbar disorders. The cross-sectional area of LF was measured using the axial images of lumbar MRI. The expression of each collagen in human surgical samples was evaluated by real-time RT-PCR and immunohistochemical analysis. To investigate the impact of inflammatory cytokines on the expression of each collagen, we treated primary human LF cells with TNF-α or IL-1β. Real-time RT-PCR analysis and immunohistochemistry showed that of the 28 types of collagen, collagen type I, III, V, VI, VIII were highly expressed regardless of LF hypertrophy. In addition, we found the moderate correlation between the cross-sectional area of LF and the mRNA expression level of collagen type I, III, and VI. In vitro analysis showed that the mRNA expression of collagen type I, III, V, VI, and VIII was up-regulated by treatment with TNF-α and with IL-1β. Our results suggested that collagen type I, III, V, VI, and VIII were the main components of the LF extracellular matrix and that collagen type I, III, and VI may serve as useful markers of LF hypertrophy. These findings may contribute to the future development of diagnostic and treatment modalities for LF hypertrophy and even LCS. Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.


Hiroki Takeda, Sota Nagai, Daiki Ikeda, Shinjiro Kaneko, Takashi Tsuji, Nobuyuki Fujita. Collagen profiling of ligamentum flavum in patients with lumbar spinal canal stenosis. Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association. 2021 Jul;26(4):560-565

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PMID: 32753253

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