ArticlePloS one2017
Fluoxetine ameliorates cartilage degradation in osteoarthritis by inhibiting Wnt/β-catenin signaling.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- DUSP26: Unveiling a critical molecular mediator and therapeutic target in developmental dysplasia of the hip‑associated secondary osteoarthritis.International journal of molecular medicine · 2026Article
- Brain-bone axis dysregulation: Biological code underlying the bidirectional association between depression and musculoskeletal disorders.Journal of orthopaedic translation · 2026Review
- Aberrant Tryptophan Metabolism Manipulates Osteochondral Homeostasis.Research (Washington, D.C.) · 2025Review
- Development of novel osteoarthritis therapy by targeting AMPK-β-catenin-Runx2 signaling.Genes & diseases · 2025Review
- The Manganese-Bone Connection: Investigating the Role of Manganese in Bone Health.Journal of clinical medicine · 2024Review
- Selective serotonin re-uptake inhibitors affect craniofacial structures in a mouse model.PloS one · 2024Article
- Overloaded axial stress activates the Wnt/β-Catenin pathway in nucleus pulposus cells of adult degenerative scoliosis combined with intervertebral disc degeneration.Molecular biology reports · 2023Article
- Small molecule inhibitors of osteoarthritis: Current development and future perspective.Frontiers in physiology · 2023Review
- Depression and Antidepressants During Pregnancy: Craniofacial Defects Due to Stem/Progenitor Cell Deregulation Mediated by Serotonin.Frontiers in cell and developmental biology · 2021Review
- Investigating correlation between self-reported clinical manifestation and synovial fluid and blood levels of Dickkopf-1 and sclerostin in patients with primary knee osteoarthritis.Clinical rheumatology · 2020Article
- Vitamin D3 protects articular cartilage by inhibiting the Wnt/β-catenin signaling pathway.Experimental and therapeutic medicine · 2020Article
- Wnt3a and wnt5a as Potential Chondrogenic Stimulators for Nucleus Pulposus Cell Induction: A Comprehensive Review.Neurospine · 2020Article
- Xanthan Gum Ameliorates Osteoarthritis and Mitigates Cartilage Degradation via Regulation of the Wnt3a/β-Catenin Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Wnt signaling: a promising target for osteoarthritis therapy.Cell communication and signaling : CCS · 2019Review
- WNT Signaling in Disease.Cells · 2019Review
- Mianserin suppresses R-spondin 2-induced activation of Wnt/β-catenin signaling in chondrocytes and prevents cartilage degradation in a rat model of osteoarthritis.Scientific reports · 2019Article
- The Metabolome and Osteoarthritis: Possible Contributions to Symptoms and Pathology.Metabolites · 2018Review
- Fluoxetine Inhibits Canonical Wnt Signaling to Impair Embryoid Body Morphogenesis: Potential Teratogenic Mechanisms of a Commonly Used Antidepressant.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- [Resveratrol regulate the extracellular matrix expression via Wnt/β-catenin pathway in nucleus pulposus cells].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abnormal activation of the Wnt/β-catenin signaling is implicated in the osteoarthritis (OA) pathology. We searched for a pre-approved drug that suppresses abnormally activated Wnt/β-catenin signaling and has a potency to reduce joint pathology in OA. We introduced the TOPFlash reporter plasmid into HCS-2/8 human chondrosarcoma cells to estimate the Wnt/β-catenin activity in the presence of 10 μM each compound in a panel of pre-approved drugs. We found that fluoxetine, an antidepressant in the class of selective serotonin reuptake inhibitors (SSRI), down-regulated Wnt/β-catenin signaling in human chondrosarcoma cells. Fluoxetine inhibited both Wnt3A- and LiCl-induced loss of proteoglycans in chondrogenically differentiated ATDC5 cells. Fluoxetine increased expression of Sox9 (the chondrogenic master regulator), and decreased expressions of Axin2 (a marker for Wnt/β-catenin signaling) and Mmp13 (matrix metalloproteinase 13). Fluoxetine suppressed a LiCl-induced increase of total β-catenin and a LiCl-induced decrease of phosphorylated β-catenin in a dose-dependent manner. An in vitro protein-binding assay showed that fluoxetine enhanced binding of β-catenin with Axin1, which is a scaffold protein forming the degradation complex for β-catenin. Fluoxetine suppressed LiCl-induced β-catenin accumulation in human OA chondrocytes. Intraarticular injection of fluoxetine in a rat OA model ameliorated OA progression and suppressed β-catenin accumulation.
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