Myofibroblast in the ligamentum flavum hypertrophic activity

Junseok W. Hur, Taegeun Bae, Sunghyeok Ye, Joo Hyun Kim, Sunhye Lee, Kyoungmi Kim, Seung Hwan Lee, Jin Soo Kim, Jang Bo Lee, Tai Hyoung Cho, Jung Yul Park, Junho K. Hur

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Purpose: Majority of the previous studies compared lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH) patients for analyses of LFH. However, the separation of normal/hypertrophied LF has often been ambiguous and the severity of hypertrophic activity differed. Here, we present a novel analysis scheme for LFH in which myofibroblast is proposed as a major etiological factor for LFH study. Methods: Seventy-one LF patient tissue samples were used for this study. Initially, mRNA levels of the samples were assessed by qRT-PCR: angiopoietin-like protein-2 (ANGPTL2), transforming growth factor-beta1 (TGF-β1), vascular endothelial growth factor (VEGF), interleukin-6, collagen-1, 3, 4, 5, and 11, and elastin. Myofibroblasts were detected by immune stain using α-smooth muscle actin (αSMA) as a marker. To study the myofibroblast in TGF-β pathway, LF tissues were analyzed for protein levels of αSMA/TGF-β1 by Western blot. In addition, from LF cells cultured with exogenous TGF-β1 conditioned medium, expression of αSMA/collagen-1 was assessed and the cell morphology was identified. Results: The comparative analysis of mRNA expression levels (LSS vs LDH) failed to show significant differences in TGF-β1 (p = 0.08); however, we found a significant positive correlation among ANGPTL2, VEGF, TGF-β1, and collagen-1 and 3, which represent common trends in hypertrophic activity (p < 0.05). We detected myofibroblast in the patient samples by αSMA staining, and the protein levels of αSMA were positively correlated with TGF-β1. In LF cell culture, exogenous TGF-β1 upregulated αSMA/collagen-1 mRNA levels and facilitated trans-differentiation to myofibroblast. Conclusions: We conclude that the transition of fibroblast to myofibroblasts via TGF-β pathway is a key linker between inflammation and fibrosis in LFH mechanism.

Original languageEnglish
Pages (from-to)2021-2030
Number of pages10
JournalEuropean Spine Journal
Volume26
Issue number8
DOIs
Publication statusPublished - 2017 Aug 1

Fingerprint

Ligamentum Flavum
Transforming Growth Factor beta1
Myofibroblasts
Smooth Muscle
Actins
Collagen
Angiopoietins
Spinal Stenosis
Messenger RNA
Vascular Endothelial Growth Factor A
Proteins
Elastin
Conditioned Culture Medium
Cultured Cells
Interleukin-6
Fibrosis
Coloring Agents
Cell Culture Techniques
Fibroblasts
Western Blotting

Keywords

  • Alpha-smooth muscle actin
  • Hypertrophy
  • Ligamentum flavum
  • Myofibroblasts
  • Transforming growth factor beta1

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine

Cite this

Hur, J. W., Bae, T., Ye, S., Kim, J. H., Lee, S., Kim, K., ... Hur, J. K. (2017). Myofibroblast in the ligamentum flavum hypertrophic activity. European Spine Journal, 26(8), 2021-2030. https://doi.org/10.1007/s00586-017-4981-2

Myofibroblast in the ligamentum flavum hypertrophic activity. / Hur, Junseok W.; Bae, Taegeun; Ye, Sunghyeok; Kim, Joo Hyun; Lee, Sunhye; Kim, Kyoungmi; Lee, Seung Hwan; Kim, Jin Soo; Lee, Jang Bo; Cho, Tai Hyoung; Park, Jung Yul; Hur, Junho K.

In: European Spine Journal, Vol. 26, No. 8, 01.08.2017, p. 2021-2030.

Research output: Contribution to journalArticle

Hur, JW, Bae, T, Ye, S, Kim, JH, Lee, S, Kim, K, Lee, SH, Kim, JS, Lee, JB, Cho, TH, Park, JY & Hur, JK 2017, 'Myofibroblast in the ligamentum flavum hypertrophic activity', European Spine Journal, vol. 26, no. 8, pp. 2021-2030. https://doi.org/10.1007/s00586-017-4981-2
Hur, Junseok W. ; Bae, Taegeun ; Ye, Sunghyeok ; Kim, Joo Hyun ; Lee, Sunhye ; Kim, Kyoungmi ; Lee, Seung Hwan ; Kim, Jin Soo ; Lee, Jang Bo ; Cho, Tai Hyoung ; Park, Jung Yul ; Hur, Junho K. / Myofibroblast in the ligamentum flavum hypertrophic activity. In: European Spine Journal. 2017 ; Vol. 26, No. 8. pp. 2021-2030.
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AU - Bae, Taegeun

AU - Ye, Sunghyeok

AU - Kim, Joo Hyun

AU - Lee, Sunhye

AU - Kim, Kyoungmi

AU - Lee, Seung Hwan

AU - Kim, Jin Soo

AU - Lee, Jang Bo

AU - Cho, Tai Hyoung

AU - Park, Jung Yul

AU - Hur, Junho K.

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N2 - Purpose: Majority of the previous studies compared lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH) patients for analyses of LFH. However, the separation of normal/hypertrophied LF has often been ambiguous and the severity of hypertrophic activity differed. Here, we present a novel analysis scheme for LFH in which myofibroblast is proposed as a major etiological factor for LFH study. Methods: Seventy-one LF patient tissue samples were used for this study. Initially, mRNA levels of the samples were assessed by qRT-PCR: angiopoietin-like protein-2 (ANGPTL2), transforming growth factor-beta1 (TGF-β1), vascular endothelial growth factor (VEGF), interleukin-6, collagen-1, 3, 4, 5, and 11, and elastin. Myofibroblasts were detected by immune stain using α-smooth muscle actin (αSMA) as a marker. To study the myofibroblast in TGF-β pathway, LF tissues were analyzed for protein levels of αSMA/TGF-β1 by Western blot. In addition, from LF cells cultured with exogenous TGF-β1 conditioned medium, expression of αSMA/collagen-1 was assessed and the cell morphology was identified. Results: The comparative analysis of mRNA expression levels (LSS vs LDH) failed to show significant differences in TGF-β1 (p = 0.08); however, we found a significant positive correlation among ANGPTL2, VEGF, TGF-β1, and collagen-1 and 3, which represent common trends in hypertrophic activity (p < 0.05). We detected myofibroblast in the patient samples by αSMA staining, and the protein levels of αSMA were positively correlated with TGF-β1. In LF cell culture, exogenous TGF-β1 upregulated αSMA/collagen-1 mRNA levels and facilitated trans-differentiation to myofibroblast. Conclusions: We conclude that the transition of fibroblast to myofibroblasts via TGF-β pathway is a key linker between inflammation and fibrosis in LFH mechanism.

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KW - Alpha-smooth muscle actin

KW - Hypertrophy

KW - Ligamentum flavum

KW - Myofibroblasts

KW - Transforming growth factor beta1

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