Myofibroblast in the ligamentum flavum hypertrophic activity
- Authors
- 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.
- Issue Date
- 8월-2017
- Publisher
- SPRINGER
- Keywords
- Ligamentum flavum; Hypertrophy; Myofibroblasts; Alpha-smooth muscle actin; Transforming growth factor beta1
- Citation
- EUROPEAN SPINE JOURNAL, v.26, no.8, pp.2021 - 2030
- Indexed
- SCIE
SCOPUS
- Journal Title
- EUROPEAN SPINE JOURNAL
- Volume
- 26
- Number
- 8
- Start Page
- 2021
- End Page
- 2030
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/82768
- DOI
- 10.1007/s00586-017-4981-2
- ISSN
- 0940-6719
- Abstract
- 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. 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-beta 1), vascular endothelial growth factor (VEGF), interleukin-6, collagen-1, 3, 4, 5, and 11, and elastin. Myofibroblasts were detected by immune stain using alpha-smooth muscle actin (alpha SMA) as a marker. To study the myofibroblast in TGF-beta pathway, LF tissues were analyzed for protein levels of alpha SMA/TGF-beta 1 by Western blot. In addition, from LF cells cultured with exogenous TGF-beta 1 conditioned medium, expression of alpha SMA/collagen-1 was assessed and the cell morphology was identified. The comparative analysis of mRNA expression levels (LSS vs LDH) failed to show significant differences in TGF-beta 1 (p = 0.08); however, we found a significant positive correlation among ANGPTL2, VEGF, TGF-beta 1, and collagen-1 and 3, which represent common trends in hypertrophic activity (p < 0.05). We detected myofibroblast in the patient samples by alpha SMA staining, and the protein levels of alpha SMA were positively correlated with TGF-beta 1. In LF cell culture, exogenous TGF-beta 1 upregulated alpha SMA/collagen-1 mRNA levels and facilitated trans-differentiation to myofibroblast. We conclude that the transition of fibroblast to myofibroblasts via TGF-beta pathway is a key linker between inflammation and fibrosis in LFH mechanism.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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