ArticlePloS one2014
Angiopoietin-like protein 2 induced by mechanical stress accelerates degeneration and hypertrophy of the ligamentum flavum in lumbar spinal canal stenosis.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- An unusual case of paraparesis due to hypertrophy of posterior longitudinal ligament at thoracic and lumbar spine with long-term follow-up: a case report and literature review.Spinal cord series and cases · 2026Review
- PPARγ signalling pathway: molecular mechanisms and therapeutic potential in ligamentum flavum hypertrophy and lumbar spinal stenosis.Journal of translational medicine · 2026Review
- Hypertrophic Ligamentum Flavum in Lumbar Spine Stenosis Is Associated With the Increased Expression of Secreted Protein Acidic and Rich in Cysteine.Global spine journal · 2024Article
- Transthyretin amyloid deposition in ligamentum flavum (LF) is significantly correlated with LF and epidural fat hypertrophy in patients with lumbar spinal stenosis.Scientific reports · 2023Article
- Mechanisms of tissue degeneration mediated by periostin in spinal degenerative diseases and their implications for pathology and diagnosis: a review.Frontiers in medicine · 2023Review
- Angiopoietin-like 2 is essential to aortic valve development in mice.Communications biology · 2022Article
- Article
- ANGPTL2 Promotes Inflammation via Integrin α5β1 in Chondrocytes.Cartilage · 2021Article
- Angptl2 is a Marker of Cellular Senescence: The Physiological and Pathophysiological Impact of Angptl2-Related Senescence.International journal of molecular sciences · 2021Review
- Fetal cervical zygapophysial joint with special reference to the associated synovial tissue: a histological study using near-term human fetuses.Anatomy & cell biology · 2021Article
- Angiopoietin-like protein 2 as a novel marker for patients with primary Sjogren's syndrome-related interstitial lung disease.Clinical and experimental medicine · 2020Article
- Development of an In Vitro 3D Model for Investigating Ligamentum Flavum Hypertrophy.Biological procedures online · 2020Article
- Angiopoietin-Like Protein 2 Induces Synovial Inflammation in the Facet Joint Leading to Degenerative Changes via Interleukin-6 Secretion.Asian spine journal · 2019Article
- Diabetes mellitus is associated with increased elastin fiber loss in ligamentum flavum of patients with lumbar spinal canal stenosis: results of a pilot histological study.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2018Article
- Interleukin 6 gene polymorphism in patients with degenerative lumbar scoliosis: a cohort study.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2018Article
- Matrix metalloproteinase promotes elastic fiber degradation in ligamentum flavum degeneration.PloS one · 2018Article
- Angiopoietin-2 promotes osteogenic differentiation of thoracic ligamentum flavum cells via modulating the Notch signaling pathway.PloS one · 2018Article
- Mechanical stress induces elastic fibre disruption and cartilage matrix increase in ligamentum flavum.Scientific reports · 2017Article
- Angiopoietin-like protein as a novel marker for liver fibrosis in chronic hepatitis B patients with normal to minimally raised ALT.BMC infectious diseases · 2017Article
- Myofibroblast in the ligamentum flavum hypertrophic activity.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2017Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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