ArticleProceedings of the National Academy of Sciences of the United States of America2020
FoxO1 is a crucial mediator of TGF-β/TAK1 signaling and protects against osteoarthritis by maintaining articular cartilage homeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Identification of therapeutic targets in osteoarthritis by combining heterogeneous transcriptional datasets, drug-induced expression profiles, and known drug-target interactions.Journal of translational medicine · 2024Pooled it
- Molecular Signature and miRNA Pattern of CD4 + T Lymphocytes in Plaque Psoriasis.Clinical reviews in allergy & immunology · 2026Review
- WuFu decoction alleviates osteoarthritis by regulating TGF-β1/Smad and ERK1/2 pathways.Histology and histopathology · 2026Article
- UCHL1 enhancesHistology and histopathology · 2026Article
- Genetic alternative splicing regulation mapping of cartilage and synovium reveals tissue-specific mechanisms of joint-related traits.Nature communications · 2026Article
- TGF-β/BMP signaling in skeletal biology: molecular mechanisms, regulatory networks, and therapeutic implications in development, regeneration, and disease.Bone research · 2026Review
- Warm Needle Acupuncture Attenuates Pain-Related Responses and Inflammation in Knee Osteoarthritis: Evidence for Involvement of TAK1/MAPK Signaling from Human Cartilage and Experimental Models.Journal of pain research · 2026Article
- Single-cell sequencing reveals a senescent immune landscape in bone marrow lesions inducing articular cartilage damage in osteoarthritis.Bone research · 2025Article
- Cytosolic phospholipase A2 as a therapeutic target for degenerative joint diseases.Bone research · 2025Article
- IRS2/FOXO1 mitigates osteoarthritis by regulating chondrocyte autophagy and mitochondrial function.Molecular medicine (Cambridge, Mass.) · 2025Article
- Recent Developments in Osteoarthritis Research: Innovative Therapeutic Approaches and the Role of Polyphenols and Nanotechnology.International journal of molecular sciences · 2025Review
- Forkhead box O proteins in chondrocyte aging and diseases.Journal of orthopaedic translation · 2025Review
- miR-320-3p regulates apelin and TGF-β/SMAD3 signaling in hypobaric hypoxia exposed rats to induce skeletal muscle atrophy.Journal of physiology and biochemistry · 2025Article
- NFIA regulates articular chondrocyte fatty acid metabolism and joint homeostasis.Science translational medicine · 2025Article
- Stem and progenitor cells in the synovial joint as targets for regenerative therapy.Nature reviews. Rheumatology · 2025Review
- LIPUS Promotes Calcium Oscillation and Enhances Calcium Dependent Autophagy of Chondrocytes to Alleviate Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Dnmt3a-mediated hypermethylation of FoxO3 promotes redox imbalance during osteoclastogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- SIRT3-PINK1-PKM2 axis prevents osteoarthritis via mitochondrial renewal and metabolic switch.Bone research · 2025Article
- Integrative analysis of the 3D genome and epigenome in mouse embryonic tissues.Nature structural & molecular biology · 2025Article
- Rethinking Osteoarthritis Management: Synergistic Effects of Chronoexercise, Circadian Rhythm, and Chondroprotective Agents.Biomedicines · 2025Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Transforming growth factor-β (TGF-β) signaling is a critical regulator for articular cartilage tissue maintenance and chondrocyte homeostasis. Nonetheless, the regulatory networks and downstream signaling pathways that govern the chondroprotective function of TGF-β in the context of osteoarthritis (OA) are not fully defined. Recent studies reveal that mice with postnatal deletion of triple forkhead box class Os (FoxOs) (1, 3, and 4) spontaneously develop OA-like pathologies. The OA phenotype largely recapitulates that observed in mice with loss of TGF-βR2. In the present study, we investigated the role of FoxOs as downstream mediators of TGF-β signaling and define their role in articular cartilage homeostasis. Among the three FoxOs (1, 3, and 4), TGF-β signaling exclusively regulates FoxO1 in a TGF-β activated kinase 1 (TAK1)-dependent manner. Furthermore, FoxO1 was genetically ablated in mice in a tissue-specific manner in articular cartilage or overexpressed in adult cartilage immediately followed by meniscal/ligament injury (MLI). Histological and microcomputed tomography (micro-CT) analyses demonstrated that loss of FoxO1 postnatally in articular cartilage leads to OA-like pathologies, and gain of FoxO1 in adult cartilage has both preventative and therapeutic effects on surgically induced OA. Mechanistically, FoxO1 was found to maintain articular chondrocyte homeostasis through induction of anabolic and autophagy-related gene expressions. Importantly, overexpression of FoxO1 markedly rescued the OA phenotypes caused by deficiency in TGF-β signaling in chondrocytes. Our study identifies that TGF-β/TAK1-FoxO1 is a key signaling cascade in regulation of articular cartilage autophagy and homeostasis and is a potentially important therapeutic target for OA-like joint diseases.
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Registered trials
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.