ArticleThe Journal of biological chemistry2015
Heavy Metal Ion Regulation of Gene Expression: MECHANISMS BY WHICH LEAD INHIBITS OSTEOBLASTIC BONE-FORMING ACTIVITY THROUGH MODULATION OF THE Wnt/β-CATENIN SIGNALING PATHWAY.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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
20 citing papers in PubMed, 39 citations in OpenAlex.
- Chronic developmental exposure to traffic-derived PMScientific reports · 2026Article
- Trace Elements-Role in Joint Function and Impact on Joint Diseases.International journal of molecular sciences · 2025Review
- Nucleic acid aptamers protect against lead (Pb(II)) toxicity.New biotechnology · 2024Article
- Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency.Journal of nanobiotechnology · 2024Article
- Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency.Research square · 2024Article
- Nucleic Acid Aptamers Protect Against Lead (Pb(II)) Toxicity.bioRxiv : the preprint server for biology · 2024Article
- Lead induced differences in bone properties in osteocalcin +/+ and -/- female mice.Bone reports · 2023Article
- Prenatal lead (Pb) exposure is associated with differential placental DNA methylation and hydroxymethylation in a human population.Epigenetics · 2022Article
- Changes in Elements and Relationships among Elements in Intervertebral Disc Degeneration.International journal of environmental research and public health · 2022Article
- Proximity to major roads and the incidence of osteoporotic fractures in elderly women: The BONE study in Beijing.Frontiers in public health · 2022Article
- The Effects of Calcium, Magnesium, Phosphorus, Fluoride, and Lead on Bone Tissue.Biomolecules · 2021Review
- Environmental Exposure to Heavy Metals Contributes to Diseases Via Deregulated Wnt Signaling Pathways.Iranian journal of pharmaceutical research : IJPR · 2021Review
- Combined exposure to formaldehyde and PMEnvironment international · 2020Article
- Cadmium and Lead Decrease Cell-Cell Aggregation and Increase Migration and Invasion in Renca Mouse Renal Cell Carcinoma Cells.International journal of molecular sciences · 2019Article
- Blood lead level: an overlooked risk of carpal tunnel syndrome in hemodialysis patients.Renal failure · 2019Article
- A Review of Metal Exposure and Its Effects on Bone Health.Journal of toxicology · 2018Review
- Sclerostin activity plays a key role in the negative effect of glucocorticoid signaling on osteoblast function in mice.Bone research · 2017Article
- Environmental Factors Impacting Bone-Relevant Chemokines.Frontiers in endocrinology · 2017Article
- Elevated Lifetime Lead Exposure Impedes Osteoclast Activity and Produces an Increase in Bone Mass in Adolescent Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- A One-Two Punch to Bone: Assessing the Combined Impact of Lead and a High-Fat Diet.Environmental health perspectives · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Exposure to lead (Pb) from environmental sources remains an overlooked and serious public health risk. Starting in childhood, Pb in the skeleton can disrupt epiphyseal plate function, constrain the growth of long bones, and prevent attainment of a high peak bone mass, all of which will increase susceptibility to osteoporosis later in life. We hypothesize that the effects of Pb on bone mass, in part, come from depression of Wnt/β-catenin signaling, a critical anabolic pathway for osteoblastic bone formation. In this study, we show that depression of Wnt signaling by Pb is due to increased sclerostin levels in vitro and in vivo. Downstream activation of the β-catenin pathway using a pharmacological inhibitor of GSK-3β ameliorates the Pb inhibition of Wnt signaling activity in the TOPGAL reporter mouse. The effect of Pb was determined to be dependent on sclerostin expression through use of the SOST gene knock-out mice, which are resistant to Pb-induced trabecular bone loss and maintain their mechanical bone strength. Moreover, isolated bone marrow cells from the sclerostin null mice show improved bone formation potential even after exposure to Pb. Also, our data suggest that the TGFβ canonical signaling pathway is the mechanism by which Pb controls sclerostin production. Taken together these results support our hypothesis that the osteoporotic-like phenotype observed after Pb exposure is, in part, regulated through modulation of the Wnt/β-catenin pathway.
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What Socratic 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 Socratic graph.