ArticleArthritis and rheumatism2012
Conditional activation of β-catenin signaling in mice leads to severe defects in intervertebral disc tissue.
Article in Arthritis and rheumatism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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66 citing papers in PubMed, 98 citations in OpenAlex.
- Deficiency of Krüppel-like factor 15 activates β-catenin and is involved in the development of osteoarthritis : Author.Arthritis research & therapy · 2026Article
- CRISPR/CasRx-mediated RNA knockdown targeting β-catenin and Ihh signaling alleviates osteoarthritis.Genes & diseases · 2025Article
- Development of novel osteoarthritis therapy by targeting AMPK-β-catenin-Runx2 signaling.Genes & diseases · 2025Review
- Emerging role and function of Hippo-YAP/TAZ signaling pathway in musculoskeletal disorders.Stem cell research & therapy · 2024Review
- Pip5k1γ promotes anabolism of nucleus pulposus cells and intervertebral disc homeostasis by activating CaMKII-Ampk pathway in aged mice.Aging cell · 2024Article
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- Intervertebral disc-intrinsic Hedgehog signaling maintains disc cell phenotypes and prevents disc degeneration through both cell autonomous and non-autonomous mechanisms.Cellular and molecular life sciences : CMLS · 2024Article
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- Vector potential dual effect of promoting the proliferation of chondrocytes and inhibiting the calcification process in the articular cartilage.Scientific reports · 2023Article
- Loss of Pinch Proteins Causes Severe Degenerative Disc Disease-Like Lesions in Mice.Aging and disease · 2023Article
- Review
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- Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain.Bone research · 2023Article
- Netrin-1 mediates nerve innervation and angiogenesis leading to discogenic pain.Journal of orthopaedic translation · 2023Article
- AMPK activator decelerates osteoarthritis development by inhibition of β-catenin signaling in chondrocytes.Journal of orthopaedic translation · 2023Article
- CRISPR-Cas9-mediated loss of function of β-catenin attenuates intervertebral disc degeneration.Molecular therapy. Nucleic acids · 2022Article
- Immuno-Modulatory Effects of Intervertebral Disc Cells.Frontiers in cell and developmental biology · 2022Review
- Relationship between Oxytocin and Osteoarthritis: Hope or Despair?International journal of molecular sciences · 2021Review
- Aberrant spinal mechanical loading stress triggers intervertebral disc degeneration by inducing pyroptosis and nerve ingrowth.Scientific reports · 2021Article
6 more citing papers are in PubMed but not listed here.
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16 authors at 7 institutions in 2 countries.
Funding
Abstract
objectiveThe incidence of low back pain is extremely high and is often linked to intervertebral disc (IVD) degeneration. The mechanism of this disease is currently unknown. This study was undertaken to investigate the role of β-catenin signaling in IVD tissue function.
methodsβ-catenin protein levels were measured by immunohistochemical analysis of disc samples obtained from patients with disc degeneration and from normal subjects. To generate β-catenin conditional activation (cAct) mice, Col2a1-CreER(T2) -transgenic mice were bred with β-catenin(fx(Ex3)/fx(Ex3)) mice. Changes in disc tissue morphology and function were examined by micro-computed tomography, histologic analysis, and real-time polymerase chain reaction assays.
resultsβ-catenin protein was up-regulated in disc tissue samples from patients with disc degeneration. To assess the effects of increased β-catenin levels on disc tissue, we generated β-catenin cAct mice. Overexpression of β-catenin in disc cells led to extensive osteophyte formation in 3- and 6-month-old β-catenin cAct mice, which were associated with significant changes in the cells and extracellular matrix of disc tissue and growth plate. Gene expression analysis demonstrated that activation of β-catenin enhanced runt-related transcription factor 2-dependent Mmp13 and Adamts5 expression. Moreover, genetic ablation of Mmp13 or Adamts5 on the β-catenin cAct background, or treatment of β-catenin cAct mice with a specific matrix metalloproteinase 13 inhibitor, ameliorated the mutant phenotype.
conclusionOur findings indicate that the β-catenin signaling pathway plays a critical role in disc tissue function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.