ArticleProceedings of the National Academy of Sciences of the United States of America2013
Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of Cyp1 enzymes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 3 of them syntheses that pooled it.
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Who cites it
67 citing papers in PubMed, 3 syntheses or guidelines pooled it, 125 citations in OpenAlex.
- Regulation of differentiation and generation of osteoclasts in rheumatoid arthritis.Frontiers in immunology · 2022Pooled it
- Polycyclic Aromatic Hydrocarbons Affect Rheumatoid Arthritis PathogenesisFrontiers in immunology · 2022Pooled it
- Meta-analysis: the effects of smoking on the disposition of two commonly used antipsychotic agents, olanzapine and clozapine.BMJ open · 2014Pooled it
- Tryptophan metabolites 3-hydroxykynurenine (3HK) and 3-hydroxyanthranilic acid (3HAA) increase oxidative stress and impair osteoblastic bone formation.The Journal of biological chemistry · 2026Article
- Gut Metabolite Indoleacrylic Acid Suppresses Osteoclast Formation by AHR mediated NF-κB Signaling Pathway.International journal of biological sciences · 2026Article
- 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
- Role of the Aryl Hydrocarbon Receptor in the Self-Renewal, Differentiation, and Immunomodulation of Adult Stem Cells.Immune network · 2025Review
- Development and validation of a nomogram for all-cause mortality in osteoporosis patients over five years.PloS one · 2025Article
- Smoking-induced suppression of β-casein in milk is associated with an increase in miR-210-5p expression in mammary epithelia.Biochemistry and biophysics reports · 2024Article
- Bridging the Gap in Understanding Bone Metastasis: A Multifaceted Perspective.International journal of molecular sciences · 2024Review
- Heavy metals, oxidative stress, and the role of AhR signaling.Toxicology and applied pharmacology · 2024Review
- 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
- Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40).Bone research · 2023Article
- AhR and CYP1B1 Control Oxygen Effects on Bone Marrow Progenitor Cells: The Enrichment of Multiple Olfactory Receptors as Potential Microbiome Sensors.International journal of molecular sciences · 2023Article
- Article
- The Potential Influence of Uremic Toxins on the Homeostasis of Bones and Muscles in Chronic Kidney Disease.Biomedicines · 2023Review
- The Association Between Clozapine Plasma Concentration, CYP2D6 (*10, *2) Polymorphisms and Risk of Adverse Reactions.Psychiatry and clinical psychopharmacology · 2023Article
- Aryl hydrocarbon receptor (AhR)-mediated signaling as a critical regulator of skeletal cell biology.Journal of molecular endocrinology · 2022Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Smoking is a major risk factor for osteoporosis and fracture, but the mechanism through which smoke causes bone loss remains unclear. Here, we show that the smoke toxins benzo(a)pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interact with the aryl hydrocarbon receptor (Ahr) to induce osteoclastic bone resorption through the activation of cytochrome P450 1a/1b (Cyp1) enzymes. BaP and TCDD enhanced osteoclast formation in bone marrow cell cultures and gavage with BaP stimulated bone resorption and osteoclastogenesis in vivo. The osteoclastogenesis triggered by BaP or RANK-L was reduced in Ahr(-/-) cells, consistent with the high bone mass noted in Ahr(-/-) male mice. The receptor activator of NF-κB ligand (RANK-L) also failed to induce the expression of Cyp1 enzymes in Ahr(-/-) cells. Furthermore, the osteoclastogenesis induced by TCDD was lower in Cyp1a1/1a2(-/-) and Cyp1a1/1a2/1b1(-/-) cultures, indicating that Ahr was upstream of the Cyp enzymes. Likewise, the pharmacological inhibition of the Cyp1 enzymes with tetramethylsilane or proadifen reduced osteoclastogenesis. Finally, deletion of the Cyp1a1, Cyp1a2, and Cyp1b1 in triple knockout mice resulted in reduced bone resorption and recapitulated the high bone mass phenotype of Ahr(-/-) mice. Overall, the data identify the Ahr and Cyp1 enzymes not only in the pathophysiology of smoke-induced osteoporosis, but also as potential targets for selective modulation by new therapeutics.
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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.