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Ambient PM2.5 Exposure and Bone Homeostasis: Analysis of UK Biobank Data and Experimental Studies in Mice and in Vitro.
- Source :
- Environmental Health Perspectives; Oct2023, Vol. 131 Issue 10, p107002-1-107002-14, 14p, 2 Charts, 5 Graphs
- Publication Year :
- 2023
-
Abstract
- BACKGROUND: Previous evidence has identified exposure to fine ambient particulate matter (PM<subscript>2.5</subscript>) as a leading risk factor for adverse health outcomes. However, to date, only a few studies have examined the potential association between long-term exposure to PM<subscript>2.5</subscript> and bone homeostasis. OBJECTIVE: We sought to examine the relationship between long-term PM<subscript>2.5</subscript> exposure and bone health and explore its potential mechanism. METHODS: This research included both observational and experimental studies. First, based on human data from UK Biobank, linear regression was used to explore the associations between long-term exposure to PM<subscript>2.5</subscript> (i.e., annual average PM<subscript>2.5</subscript> concentration for 2010) and bone mineral density [BMD; i.e., heel BMD (푛= 37,440) and femur neck and lumbar spine BMD (푛= 29,766)], which were measured during 2014-2020. For the experimental animal study, C57BL/6 male mice were assigned to ambient PM<subscript>2.5</subscript> or filtered air for 6 months via a whole-body exposure system. Micro-computed tomography analyses were applied to measure BMD and bone microstructures. Biomarkers for bone turnover and inflammation were examined with histological staining, immunohistochemistry staining, and enzyme-linked immunosorbent assay. We also performed tartrate-resistant acid phosphatase (TRAP) staining and bone resorption assay to determine the effect of PM<subscript>2.5</subscript> exposure on osteoclast activity in vitro. In addition, the potential downstream regulators were assessed by real-time polymerase chain reaction and western blot. RESULTS: We observed that long-term exposure to PM<subscript>2.5</subscript> was significantly associated with lower BMD at different anatomical sites, according to the analysis of UK Biobank data. In experimental study, mice exposed long-term to PM<subscript>2.5</subscript> exhibited excessive osteoclastogenesis, dysregulated osteogenesis, higher tumor necrosis factor-alpha (TNF-α) expression, and shorter femur length than control mice, but they demonstrated no significant differences in femur structure or BMD. In vitro, cells stimulated with conditional medium of PM<subscript>2.5</subscript>-stimulated macrophages had aberrant osteoclastogenesis and differences in the protein/mRNA expression of members of the TNF-α/Traf6/c-Fos pathway, which could be partially rescued by TNF-α inhibition. DISCUSSION: Our prospective observational evidence suggested that long-term exposure to PM<subscript>2.5</subscript> is associated with lower BMD and further experimental results demonstrated exposure to PM<subscript>2.5</subscript> could disrupt bone homeostasis, which may be mediated by inflammation-induced osteoclastogenesis. [ABSTRACT FROM AUTHOR]
- Subjects :
- HYDROCARBON analysis
METAL analysis
AIR pollution
PARTICULATE matter
HOMEOSTASIS
IN vitro studies
REVERSE transcriptase polymerase chain reaction
BONES
SCIENTIFIC observation
INFLAMMATION
ANIMAL experimentation
IMMUNOHISTOCHEMISTRY
MULTIPLE regression analysis
WESTERN immunoblotting
ONE-way analysis of variance
QUANTITATIVE research
COMPARATIVE studies
T-test (Statistics)
DESCRIPTIVE statistics
RESEARCH funding
ENZYME-linked immunosorbent assay
DATA analysis software
COMPUTED tomography
MICE
LONGITUDINAL method
Subjects
Details
- Language :
- English
- ISSN :
- 00916765
- Volume :
- 131
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Environmental Health Perspectives
- Publication Type :
- Academic Journal
- Accession number :
- 173464136
- Full Text :
- https://doi.org/10.1289/EHP11646