ArticleInternational journal of molecular sciences2020
Kynurenine Promotes RANKL-Induced Osteoclastogenesis In Vitro by Activating the Aryl Hydrocarbon Receptor Pathway.
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, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- The tryptophan catabolite or kynurenine pathway in COVID-19 and critical COVID-19: a systematic review and meta-analysis.BMC infectious diseases · 2022Pooled it
- The gut-bone axis: microbial metabolism and nutritional interventions for bone health.Gut microbes · 2026Review
- Tryptophan metabolites 3-hydroxykynurenine (3HK) and 3-hydroxyanthranilic acid (3HAA) increase oxidative stress and impair osteoblastic bone formation.The Journal of biological chemistry · 2026Article
- Nutrients and Metabolites as Signalling Molecules in Osteoclasts.Current osteoporosis reports · 2026Review
- The gut-bone axis: mechanisms through which oleic acid regulates bone metabolism and its potential in preventing and treating osteoporosis.Frontiers in nutrition · 2026Review
- Progression and Metastasis of Lung Cancer: Clinical Features, Molecular Mechanisms, and Clinical Managements.MedComm · 2025Review
- Lipid metabolism in age-related musculoskeletal disorders: insights into sarcopenia and osteoporosis.BMC biology · 2025Review
- Inhibition of AhR improves cortical bone and skeletal muscle function via preservation of neuromuscular junctions.JCI insight · 2025Article
- Expression of the aryl hydrocarbon receptor in Osterix-lineage cells regulates adult skeletal homeostasis in a compartment-specific manner.JBMR plus · 2025Article
- Aberrant Tryptophan Metabolism Manipulates Osteochondral Homeostasis.Research (Washington, D.C.) · 2025Review
- Deciphering the gut microbiome's metabolic code: pathways to bone health and novel therapeutic avenues.Frontiers in endocrinology · 2025Review
- Association Between Dietary Tryptophan Intake and Bone Health: A Cross-Sectional Study.Calcified tissue international · 2024Article
- Clofazimine inhibits small-cell lung cancer progression by modulating the kynurenine/aryl hydrocarbon receptor axis.International journal of biological macromolecules · 2024Article
- Article
- Bridging the Gap in Understanding Bone Metastasis: A Multifaceted Perspective.International journal of molecular sciences · 2024Review
- The Role of Aryl Hydrocarbon Receptor in Bone Biology.International journal of tryptophan research : IJTR · 2024Review
- The role of aryl hydrocarbon receptor in the occurrence and development of periodontitis.Frontiers in immunology · 2024Review
- Amino Acid Metabolism in Bone Metastatic Disease.Current osteoporosis reports · 2023Review
- Article
- The Role of the Kynurenine Pathway in the Pathophysiology of Frailty, Sarcopenia, and Osteoporosis.Nutrients · 2023Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
There is increasing evidence of the involvement of the tryptophan metabolite kynurenine (KYN) in disrupting osteogenesis and contributing to aging-related bone loss. Here, we show that KYN has an effect on bone resorption by increasing osteoclastogenesis. We have previously reported that in vivo treatment with KYN significantly increased osteoclast number lining bone surfaces. Here, we report the direct effect of KYN on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in Raw 264.7 macrophage cells, and we propose a potential mechanism for these KYN-mediated effects. We show that KYN/RANKL treatment results in enhancement of RANKL-induced osteoclast differentiation. KYN drives upregulation and activation of the key osteoclast transcription factors, c-fos and NFATc1 resulting in an increase in the number of multinucleated TRAP+ osteoclasts, and in hydroxyapatite bone resorptive activity. Mechanistically, the KYN receptor, aryl hydrocarbon receptor (AhR), plays an important role in the induction of osteoclastogenesis. We show that blocking AhR signaling using an AhR antagonist, or AhR siRNA, downregulates the KYN/RANKL-mediated increase in c-fos and NFATc1 and inhibits the formation of multinucleated TRAP + osteoclasts. Altogether, this work highlights that the novelty of the KYN and AhR pathways might have a potential role in helping to regulate osteoclast function with age and supports pursuing additional research to determine if they are potential therapeutic targets for the prevention or treatment of osteoporosis.
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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.