ArticleInternational journal of molecular sciences2020
Concentration and Duration of Indoxyl Sulfate Exposure Affects Osteoclastogenesis by Regulating NFATc1 via Aryl Hydrocarbon Receptor.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 34 citations in OpenAlex.
- The gut-bone axis: microbial metabolism and nutritional interventions for bone health.Gut microbes · 2026Review
- Mineral and Bone Disease in CKD and Kidney Transplantation: Controversies, Gaps, and a Path Forward.Kidney international reports · 2026Review
- Article
- Gut microbiota in chronic kidney disease-mineral and bone disorder: shared mechanisms, disease-specific signatures, and therapeutic prospects.Frontiers in endocrinology · 2026Review
- The uremic toxin indoxyl sulfate decreases osteocyte RANKL/OPG and increases Wnt inhibitor RNA expression that is reversed by PTH.JBMR plus · 2025Article
- Redefining Roles: A Paradigm Shift in Tryptophan-Kynurenine Metabolism for Innovative Clinical Applications.International journal of molecular sciences · 2024Review
- Uremic Toxin Receptor AhR Facilitates Renal Senescence and Fibrosis via Suppressing Mitochondrial Biogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Uremic toxins mediate kidney diseases: the role of aryl hydrocarbon receptor.Cellular & molecular biology letters · 2024Review
- Resveratrol Mitigates Uremic Toxin-Induced Intestinal Barrier Dysfunction in Chronic Kidney Disease by Promoting Mitophagy and Inhibiting Apoptosis Pathways.International journal of medical sciences · 2024Article
- The role of aryl hydrocarbon receptor in the occurrence and development of periodontitis.Frontiers in immunology · 2024Review
- The Role of Aryl Hydrocarbon Receptor in Bone Biology.International journal of tryptophan research : IJTR · 2024Review
- The Dietary Fiber Inulin Slows Progression of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) in a Rat Model of CKD.JBMR plus · 2023Article
- The Potential Influence of Uremic Toxins on the Homeostasis of Bones and Muscles in Chronic Kidney Disease.Biomedicines · 2023Review
- Role of Calcimimetics in Treating Bone and Mineral Disorders Related to Chronic Kidney Disease.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Indoleamine 2,3-Dioxygenase 1 Deletion-Mediated Kynurenine Insufficiency in Vascular Smooth Muscle Cells Exacerbates Arterial Calcification.Circulation · 2022Article
- Ongoing Clinical Trials in Aging-Related Tissue Fibrosis and New Findings Related to AhR Pathways.Aging and disease · 2022Review
- Salivary microbiota of periodontitis aggravates bone loss in ovariectomized rats.Frontiers in cellular and infection microbiology · 2022Article
- Inhibition of Human Osteoclast Differentiation by Kynurenine through the Aryl-Hydrocarbon Receptor Pathway.Cells · 2021Article
- Peripheral Blood Mononuclear Cells (PBMCs) to Dissect the Underlying Mechanisms of Bone Disease in Chronic Kidney Disease and Rare Renal Diseases.Current osteoporosis reports · 2021Review
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 1 country.
Funding
Abstract
Indoxyl sulfate (IS) is a chronic kidney disease (CKD)-specific renal osteodystrophy metabolite that affects the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a transcription factor promoting osteoclastogenesis. However, the mechanisms underlying the regulation of NFATc1 by IS remain unknown. It is intriguing that the Aryl hydrocarbon receptor (AhR) plays a key role in osteoclastogenesis, since IS is an endogenous AhR agonist. This study investigates the relationship between IS concentration and osteoclast differentiation in Raw 264.7 cells, and examines the effects of different IS concentrations on NFATc1 expression through AhR signaling. Our data suggest that both osteoclastogenesis and NFATc1 are affected by IS through AhR signaling in both dose- and time-dependent manners. Osteoclast differentiation increases with short-term, low-dose IS exposure and decreases with long-term, high-dose IS exposure. Different IS levels switch the role of AhR from that of a ligand-activated transcription factor to that of an E3 ubiquitin ligase. We found that the AhR nuclear translocator may play an important role in the regulation of these dual functions of AhR under IS treatment. Altogether, this study demonstrates that the IS/AhR/NFATc1 signaling axis plays a critical role in osteoclastogenesis, indicating a potential role of AhR in the pathology and abnormality of bone turnover in CKD patients.
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