Dataset Information

Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum.

ABSTRACT: Lumbar spinal stenosis (LSS) is one of the most frequent causes of low back pain and gait disturbance in the elderly. Ligamentum flavum (LF) hypertrophy is the main pathomechanism of LSS, but the reason for its occurrence is not clearly elucidated. In this study, we established a novel animal model of intervertebral mechanical stress concentration and investigated the biological property of the LF. The LF with mechanical stress concentration showed degeneration with elastic fibres disruption and cartilage matrix increase, which are similar to the findings in hypertrophied LF from patients with LSS. By contrast, decreased Col2a1 expression was found in the LF at fixed levels, in which mechanical stress was strongly reduced. These findings indicate that mechanical stress plays a crucial role in LF hypertrophy through cartilage matrix increase. The findings also suggest that fusion surgery, which eliminates intervertebral instability, may change the property of the LF and lead to the relief of patients' symptoms.

SUBMITTER: Hayashi K

PROVIDER: S-EPMC5638934 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum.

Hayashi Kazunori K Suzuki Akinobu A Abdullah Ahmadi Sayed S Terai Hidetomi H Yamada Kentaro K Hoshino Masatoshi M Toyoda Hiromitsu H Takahashi Shinji S Tamai Koji K Ohyama Shoichiro S Javid Akgar A Suhrab Rahmani Mohammad M Hasib Maruf Mohammad MM Nakamura Hiroaki H

Scientific reports 20171012 1

Lumbar spinal stenosis (LSS) is one of the most frequent causes of low back pain and gait disturbance in the elderly. Ligamentum flavum (LF) hypertrophy is the main pathomechanism of LSS, but the reason for its occurrence is not clearly elucidated. In this study, we established a novel animal model of intervertebral mechanical stress concentration and investigated the biological property of the LF. The LF with mechanical stress concentration showed degeneration with elastic fibres disruption and ...[more]

PMID: 29026131

Similar Datasets

Project description:The present study aimed to screen crucial micro (mi)RNAs and long non‑coding (lnc)RNAs involved in the development of ossification of ligamentum flavum (OLF) based on the miRNA‑mRNA and lncRNA‑miRNA‑mRNA competing endogenous (ce)RNA regulatory network analyses, which are rarely reported. The differentially expressed genes (DEGs), differentially expressed lncRNAs (DELs) and differentially expressed miRNAs (DEMs) between 4 OLF and 4 healthy controls were identified using two microarray datasets GSE106253 and GSE106256 collected from the Gene Expression Omnibus database. A protein‑protein interaction (PPI) network was constructed, followed by calculation of topological characteristics and sub‑module analysis in order to obtain hub DEGs. The miRNA‑mRNA and lncRNA‑miRNA networks that were established based on their interaction pairs, obtained from miRwalk and starBase databases, respectively, were integrated to form the ceRNA network. The underlying functions of mRNAs were predicted using the Database for Annotation, Visualization and Integrated Discovery (DAVID). The present study screened 828 DEGs, 119 DELs and 81 DEMs between OLF and controls. PPI network and module analyses identified interleukin (IL)10, adenylate cyclase (ADCY)5, suppressor of cytokine signaling (SOCS)3, G protein subunit gamma (GNG) 4, collagen type II α 1 chain (COL2A1) and collagen type XIII α 1 chain (COL13A1) as hub genes. The miRNA‑mRNA network analysis demonstrated IL10 could be regulated by miR‑210‑3p, while COL13A1 and COL2A1 could be modulated by miR‑329‑3p and miR‑222‑5p, respectively. lncRNA‑miRNA‑mRNA ceRNA network analysis identified that small nucleolar RNA host gene 16‑hsa‑miR‑196a‑5p‑SOCS3, ankyrin repeat and SOCS box containing 16‑AS1‑hsa‑miR‑379‑5p‑GNG4, nuclear enriched abundant transcript 1‑has‑miR‑181b‑5p‑ADCY5, rhophilin 1‑AS1‑hsa‑miR‑299‑3p‑WNT7B interaction axes may be crucial. DAVID analysis predicted IL10, ADCY5, GNG4 and SOCS3 were involved in 'adaptive immune response', 'Chemokine signaling pathway' and 'regulation of apoptosis' processes, while COL2A1, COL13A1 and WNT7B may be ossification related. In conclusion, the identification of these crucial miRNAs and lncRNAs may be conducive for explaining the pathogenesis of OLF and provide certain natural, endogenous and nontoxic drug targets for the treatment of OLF.

Project description:Chronic inflammation and subsequent fibrosis induced by mechanical stress play an important role in ligamentum flavum (LF) hypertrophy and degeneration in patients with lumbar spinal canal stenosis (LSCS). Angiopoietin-like protein 2 (Angptl2) is a chronic inflammatory mediator induced under various pathological conditions and increases the expression of TGF-β1, which is a well-characterized mediator in LF hypertrophy. We investigated whether Angptl2 is induced by mechanical stress, and whether it contributes to LF hypertrophy and degeneration by activating the TGF-β1 signaling cascade. In this study, we investigated human LF tissue and LF fibroblasts isolated from patients who underwent lumbar surgery. We found that Angptl2 was abundantly expressed in fibroblasts of hypertrophied LF tissues at both the mRNA and protein levels. This expression was not only positively correlated with LF thickness and degeneration but also positively correlated with lumbar segmental motion. Our in vitro experiments with fibroblasts from hypertrophied LF tissue revealed that mechanical stretching stress increases the expression and secretion of Angptl2 via activation of calcineurin/NFAT pathways. In hypertrophied LF tissue, expression of TGF-β1 mRNA was also increased and TGF-β1/Smad signaling was activated. Angptl2 expression in LF tissue was positively correlated with the expression of TGF-β1 mRNA, suggesting cooperation between Angptl2 and TGF-β1 in the pathogenesis of LF hypertrophy. In vitro experiments revealed that Angptl2 increased levels of TGF-β1 and its receptors, and also activated TGF-β1/Smad signaling. Mechanical stretching stress increased TGF-β1 mRNA expression, which was partially attenuated by treatment with a calcineurin/NFAT inhibitor or Angptl2 siRNA, indicating that induction of TGF-β1 expression by mechanical stretching stress is partially mediated by Angptl2. We conclude that expression of Angptl2 induced by mechanical stress in LF fibroblasts promotes LF tissue degeneration by activation of TGF-β1/Smad signaling, which results in LF hypertrophy in patients with LSCS.

Dataset Information

Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum.

Publications

Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets