Journal
ENVIRONMENTAL HEALTH PERSPECTIVES
Volume 121, Issue 1, Pages 97-104Publisher
US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
DOI: 10.1289/ehp.1205374
Keywords
bone mineral density; lead; mesenchymal stem cells; rat; Wnt signaling
Funding
- National Institutes of Health (NIH) [P30AR061307]
- Public Health Service grants [NIH T32 ES07026, R01 ES012712, T32 AR053459, P01 ES011854, P30 ES301247]
Ask authors/readers for more resources
BACKGROUND: Exposure to lead (Pb) from environmental and industrial sources remains an overlooked serious public health risk. Elucidating the effect of Pb on bone cell function is therefore critical for understanding its risk associated with diseases of low bone mass. OBJECTIVES: We tested the hypothesis that Pb negatively affects bone mass. We also assessed the under-lying mechanisms of Pb on bone signaling pathways. METHODS: We used a model of low-level Pb exposure in a rodent beginning before conception and continuing over 18 months. We characterized the effect of Pb on bone quality using dual-energy X-ray absorptiometry (DXA), micro-computed tomography, Raman spectroscopy, and histology. We assessed the effect of Pb on bone and adipocyte formation by mineral deposition, lipid droplet formation, and Western blot and RNA analysis. RESULTS: Pb-exposed animals had decreased bone mass that resulted in bones that were more susceptible to fracture. Pb decreased osteoblastic cell number leading to a depression of bone formation. Accompanying this, Pb exposure elevated sclerostin protein levels in the skeleton, and correspondingly reduced levels of beta-catenin and Runx2 in stromal precursor cells. Pb also increased skeletal expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). These results indicate a shift in mesenchymal differentiation wherein Pb promoted enhanced adipo-genesis and decreased osteoblasto-genesis. Substantial differences in bone marrow composition were observed, highlighted by an increase in adipocytes. CONCLUSIONS: The disruption Pb has on bone mass and bone homeostasis is principally explained by inhibition of the Wnt/beta-catenin pathway, which may provide a molecular basis for novel therapeutic strategies to combat Pb-induced bone pathologies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available