ArticlePloS one2014
Verapamil protects against cartilage degradation in osteoarthritis by inhibiting Wnt/β-catenin signaling.
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 56 papers.
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Who cites it
56 citing papers in PubMed, 82 citations in OpenAlex.
- Metabolic disorders and osteoarthritis: novel insights into pathological mechanisms and therapeutic strategies.Life medicine · 2026Review
- YTHDF2-driven degradation of BARX2 mRNA accelerates osteoarthritis progression by enhancing the TOP2A/WNT/β-Catenin axis.Communications biology · 2026Article
- PIEZO mechanosensitivity in chondrocytes is differentially modulated by L-type and T-type voltage-sensitive ion channels.Osteoarthritis and cartilage open · 2026Article
- The gut‑bone‑cartilage triad: Microbial regulation of the Wnt/β‑catenin signaling pathway in osteoarthritis joint remodeling (Review).Molecular medicine reports · 2026Review
- Insights from pharmacovigilance databases, clinical cohorts and preclinical models into VEGF(R) inhibitor-induced arthritis in cancer.Communications medicine · 2025Article
- Ion channels as therapeutic targets in osteoarthritis.Trends in pharmacological sciences · 2025Review
- Wnt/β-catenin regulates Gli1 + osteogenic progenitors in condylar subchondral bone development and osteoarthritis.BMC musculoskeletal disorders · 2025Article
- Exploring the Multifactorial Regulation of PIEZO1 in Chondrocytes: Mechanisms and Implications.International journal of medical sciences · 2025Review
- Development of novel osteoarthritis therapy by targeting AMPK-β-catenin-Runx2 signaling.Genes & diseases · 2025Review
- Ion channels in osteoarthritis: emerging roles and potential targets.Nature reviews. Rheumatology · 2024Review
- A brief review of current treatment options for osteoarthritis including disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics.Annals of medicine and surgery (2012) · 2024Review
- Antihypertensive drug-associated adverse events in osteoarthritis: a study of a large real-world sample based on the FAERS database.Frontiers in pharmacology · 2024Article
- Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors.International journal of molecular sciences · 2023Article
- Evaluation of Cartilage Integrity Following Administration of Oral and Intraarticular Nifedipine in a Murine Model of Osteoarthritis.Biomedicines · 2023Article
- Examining Mechanisms for Voltage-Sensitive Calcium Channel-Mediated Secretion Events in Bone Cells.Calcified tissue international · 2023Review
- Biomarkers of Osteoarthritis-A Narrative Review on Causal Links with Metabolic Syndrome.Life (Basel, Switzerland) · 2023Review
- Recent Advances in Small Molecule Inhibitors for the Treatment of Osteoarthritis.Journal of clinical medicine · 2023Review
- The role of PIEZO ion channels in the musculoskeletal system.American journal of physiology. Cell physiology · 2023Review
- Osteoarthritis: pathogenic signaling pathways and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Altered Extracellular Matrix as an Alternative Risk Factor for Epileptogenicity in Brain Tumors.Biomedicines · 2022Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In past years, the canonical Wnt/β-catenin signaling pathway has emerged as a critical regulator of cartilage development and homeostasis. FRZB, a soluble antagonist of Wnt signaling, has been studied in osteoarthritis (OA) animal models and OA patients as a modulator of Wnt signaling. We screened for FDA-approved drugs that induce FRZB expression and suppress Wnt/β-catenin signaling. We found that verapamil, a widely prescribed L-type calcium channel blocker, elevated FRZB expression and suppressed Wnt/β-catenin signaling in human OA chondrocytes. Expression and nuclear translocation of β-catenin was attenuated by verapamil in OA chondrocytes. Lack of the verapamil effects in LiCl-treated and FRZB-downregulated OA chondrocytes also suggested that verpamil suppressed Wnt signaling by inducing FRZB. Verapamil enhanced gene expressions of chondrogenic markers of ACAN encoding aggrecan, COL2A1 encoding collagen type II α1, and SOX9, and suppressed Wnt-responsive AXIN2 and MMP3 in human OA chondrocytes. Verapamil ameliorated Wnt3A-induced proteoglycan loss in chondrogenically differentiated ATDC5 cells. Verapamil inhibited hypertrophic differentiation of chondrocytes in the explant culture of mouse tibiae. Intraarticular injection of verapamil inhibited OA progression as well as nuclear localizations of β-catenin in a rat OA model. We propose that verapamil holds promise as a potent therapeutic agent for OA by upregulating FRZB and subsequently downregulating Wnt/β-catenin signaling.
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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.