RESUMO
The objective of the present study was to review the molecular mechanisms of the adverse effects of environmental pollutants on chondrocytes and extracellular matrix (ECM). Existing data demonstrate that both heavy metals, including cadmium (Cd), lead (Pb), and arsenic (As), as well as organic pollutants, including polychlorinated dioxins and furans (PCDD/Fs) and polychlorinated biphenyls (PCB), bisphenol A, phthalates, polycyclic aromatic hydrocarbons (PAH), pesticides, and certain other organic pollutants that target cartilage ontogeny and functioning. Overall, environmental pollutants reduce chondrocyte viability through the induction apoptosis, senescence, and inflammatory response, resulting in cell death and impaired ECM production. The effects of organic pollutants on chondrocyte development and viability were shown to be mediated by binding to the aryl hydrocarbon receptor (AhR) signaling and modulation of non-coding RNA expression. Adverse effects of pollutant exposures were observed in articular and growth plate chondrocytes. These mechanisms also damage chondrocyte precursors and subsequently hinder cartilage development. In addition, pollutant exposure was shown to impair chondrogenesis by inhibiting the expression of Sox9 and other regulators. Along with altered Runx2 signaling, these effects also contribute to impaired chondrocyte hypertrophy and chondrocyte-to-osteoblast trans-differentiation, resulting in altered endochondral ossification. Several organic pollutants including PCDD/Fs, PCBs and PAHs, were shown to induce transgenerational adverse effects on cartilage development and the resulting skeletal deformities. Despite of epidemiological evidence linking human environmental pollutant exposure to osteoarthritis or other cartilage pathologies, the data on the molecular mechanisms of adverse effects of environmental pollutant exposure on cartilage tissue were obtained from studies in laboratory rodents, fish, or cell cultures and should be carefully extrapolated to humans, although they clearly demonstrate that cartilage should be considered a putative target for environmental pollutant toxicity.
RESUMO
An increasing body of literature has demonstrated that armed conflicts and military activity may contribute to environmental pollution with metals, although the existing data are inconsistent. Therefore, in this paper, we discuss potential sources of military-related metal emissions, environmental metal contamination, as well as routes of metal exposure and their health hazards in relation to military activities. Emission of metals into the environment upon military activity occurs from weapon residues containing high levels of particles containing lead (Pb; leaded ammunition), copper (Cu; unleaded), and depleted uranium (DU). As a consequence, military activity results in soil contamination with Pb and Cu, as well as other metals including Cd, Sb, Cr, Ni, Zn, with subsequent metal translocation to water, thus increasing the risk of human exposure. Biomonitoring studies have demonstrated increased accumulation of metals in plants, invertebrates, and vertebrate species (fish, birds, mammals). Correspondingly, military activity is associated with human metal exposure that results from inhalation or ingestion of released particles, as well as injuries with subsequent metal release from embedded fragments. It is also notable that local metal accumulation following military injury may occur even without detectable fragments. Nonetheless, data on health effects of military-related metal exposures have yet to be systematized. The existing data demonstrate adverse neurological, cardiovascular, and reproductive outcomes in exposed military personnel. Moreover, military-related metal exposures also result in adverse neurodevelopmental outcome in children living within adulterated territories. Experimental in vivo and in vitro studies also demonstrated toxic effects of specific metals as well as widely used metal alloys, although laboratory data report much wider spectrum of adverse effects as compared to epidemiological studies. Therefore, further epidemiological, biomonitoring and laboratory studies are required to better characterize military-related metal exposures and their underlying mechanisms of their adverse toxic effects.
