ArticleNutrients2022
Trimethylamine-N-Oxide Promotes Osteoclast Differentiation and Bone Loss via Activating ROS-Dependent NF-κB Signaling Pathway.
Article in Nutrients, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Gut microbiome and bone health: update on mechanisms, clinical correlations, and possible treatment strategies.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Pooled it
- Quercetin-derived carbon dots-modified ZIF-8 and M2 macrophage-derived migrasomes-functionalized microenvironment-responsive nanocomposite hydrogel for osteoporotic bone defects regeneration.Bioactive materials · 2027Article
- Targeting the gut-bone axis in osteoporosis: probiotic interventions and other microbiota-based therapeutic strategies.Gut microbes · 2026Review
- The gut-bone axis: microbial metabolism and nutritional interventions for bone health.Gut microbes · 2026Review
- Review
- Metabolic messengers from the gut to the joint: Toward precision management of osteoarthritis (Review).International journal of molecular medicine · 2026Review
- β-cell FMO3-produced TMAO prevents NF-κB-mediated senescence and inflammation in ageing and diabetic conditions.Nature communications · 2026Article
- Gut Microbiota-Derived TMAO Drives MC3T3-E1 Senescence and Osteogenic Dysfunction via cGAS-STING-NF-κB Signaling: Implications for Age-Related Bone Loss.Calcified tissue international · 2026Article
- Targeting the gut‑bone axis through exercise: A novel approach to osteoporosis prevention and treatment (Review).International journal of molecular medicine · 2026Review
- Article
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- Roles of gut metabolites on bone mineralization and remodeling: impact of metabolic dysregulation on the gut-immune-bone axis.Frontiers in endocrinology · 2026Review
- Associations of Dietary and Circulating Choline and Glycine With Bone Mineral Density: UK Biobank Analyses With Mendelian Randomization.International journal of endocrinology · 2026Article
- Moderate-intensity treadmill exercise attenuates osteoporotic bone loss in ovariectomized mice via modulation of gut microbiota and glycerophospholipid metabolism.Frontiers in physiology · 2026Article
- Microbial mechanisms and therapeutic interventions in the periodontitis-inflammatory bowel disease axis: a comprehensive review.Journal of oral microbiology · 2026Review
- Perennial ryegrass improves bone quality in geese: insights from the gut-bone axis.AMB Express · 2025Article
- Gut microbiota-derived TMAO drives the kidney-bone-vascular axis in chronic kidney disease complications.Renal failure · 2025Review
- High-fat diet, intestinal microecology and bone loss.Nutrition & metabolism · 2025Review
- Nrf2 signaling pathway: focus on oxidative stress in osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Review
- Licochalcone D inhibits osteoclast differentiation and postmenopausal osteoporosis by inactivating the NF-κB signaling pathway.Journal of orthopaedic surgery and research · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Trimethylamine-N-oxide (TMAO), an important gut microbiota (GM)-derived metabolite, has been shown to be abnormally increased in osteoporosis. However, the role and underlying mechanism of TMAO in regulating bone loss during osteoporosis have not been fully investigated. In the current study, we found that 100-400 μM TMAO dose-dependently enhanced TRAP-positive osteoclasts, F-actin ring formation, and resorption area on bovine bone slices and up-regulated osteoclast-related gene expression (Calcr, Traf6, Dcstamp, Acp5, C-Fos, and NFATc1). Western blotting validated that TMAO not only activated NF-κB signaling pathway but also stimulated c-Fos and NFATc1 protein expression in a dose-dependent manner. Furthermore, BAY 11-7082, an NF-κB inhibitor, pretreatment markedly suppressed TRAP-positive osteoclast formation and osteoclast-related genes under TMAO treatment. BAY 11-7082 also inhibited p-p65/p65, c-Fos, and NFATc1 protein expression promoted by TMAO. Moreover, TMAO significantly increased ROS production, which was inhibited by N-acetylcysteine (NAC), an ROS antagonist. In addition, we proved that NAC pretreatment could inhibit TMAO-promoted NF-κB activation. NAC also suppressed TRAP-positive osteoclast formation, osteoclast-related gene expression, and protein expression of c-Fos and NFATc1 under TMAO treatment. In vivo studies showed significantly decreased bone mass and increased TRAP-positive osteoclasts in TMAO-treated C57BL/6 mice. Moreover, western-blotting and immunohistochemical staining showed that TMAO administration markedly stimulated NF-κB p65 expression. Additionally, TMAO administration significantly promoted the gene and protein expression of C-Fos and NFATc1. In conclusion, TMAO could promote osteoclast differentiation and induce bone loss in mice by activating the ROS-dependent NF-κB signaling pathway.
Indexed as
Identifiers
What OpenQuestion holds
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.