Prevalence of rheumatoid arthritis in relation to serum cadmium concentrations: cross-sectional study using Korean National Health and Nutrition Examination Survey (KNHANES) data

Joo, Sang Hyun; Lee, Joongyub; Hutchinson, David; Song, Yeong Wook

doi:10.1136/bmjopen-2018-023233

Cited by 24 publications

(14 citation statements)

References 47 publications

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“…Conversely, administration of hormones such as oral contraceptives, which contain progesterone and oestrogen, seems to increase serum copper and ceruloplasmin levels in humans and rats, while hepatic zinc stores are elevated [ 83 ]. In a large cross-sectional study of the Korean National Health and Nutritional Examination Survey, RA in females was associated with increased cadmium in sera [ 84 ]. Cadmium can be an endocrine disruptor and considered a “metallo-oestrogen” because of its oestrogenic actions.…”

Section: Zinc and Cadmium In The Aetiology And As Risk Factors Of mentioning

confidence: 99%

Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis

Frangos

Maret

2020

Nutrients

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Osteoarthritis (OA) and rheumatoid arthritis (RA) are inflammatory articular conditions with different aetiology, but both result in joint damage. The nutritionally essential metal zinc (Zn2+) and the non-essential metal cadmium (Cd2+) have roles in these arthritic diseases as effectors of the immune system, inflammation, and metabolism. Despite both metal ions being redox-inert in biology, they affect the redox balance. It has been known for decades that zinc decreases in the blood of RA patients. It is largely unknown, however, whether this change is only a manifestation of an acute phase response in inflammation or relates to altered availability of zinc in tissues and consequently requires changes of zinc in the diet. As a cofactor in over 3000 human proteins and as a signaling ion, zinc affects many pathways relevant for arthritic disease. How it affects the diseases is not just a question of zinc status, but also an issue of mutations in the many proteins that maintain cellular zinc homoeostasis, such as zinc transporters of the ZIP (Zrt-/Irt-like protein) and ZnT families and metallothioneins, and the multiple pathways that change the expression of these proteins. Cadmium interferes with zinc’s functions and there is increased uptake under zinc deficiency. Remarkably, cadmium exposure through inhalation is now recognized in the activation of macrophages to a pro-inflammatory state and suggested as a trigger of a specific form of nodular RA. Here, we discuss how these metal ions participate in the genetic, metabolic, and environmental factors that lead to joint destruction. We conclude that both metal ions should be monitored routinely in arthritic disease and that there is untapped potential for prognosis and treatment.

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Section: Zinc and Cadmium In The Aetiology And As Risk Factors Of mentioning

confidence: 99%

Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis

Frangos

Maret

2020

Nutrients

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“…At first glance it seem unlikely that mercury is responsible for this link since only a small amount of mercury is present in cigarette smoke (39). However, the large amount of cadmium in cigarette smoke (40) may be relevant, since cadmium exposure is a proposed risk factor for rheumatoid arthritis (41), and synergistic actions between toxic metals such as cadmium and mercury are recognized (42). Cadmium and mercury from cigarette smoke could therefore accentuate each other's toxicity within the synovium.…”

Section: Discussionmentioning

confidence: 99%

“…To obtain more evidence that toxic metals could trigger connective tissue diseases, further studies using this toxicant model could be combined with strains of mice that are genetically susceptible to develop an autoimmune reaction to mercury (21), with mice exposed to cigarette smoke (38), or with mice on a low selenium diet which could potentiate mercury toxicity (85). In addition, other metal toxicants such as lead (86) and cadmium (41) could be studied for their effects on connective tissues. In the case of osteoarthritis, this toxicant model could be used to see if osteoarthritis develops earlier than expected in genetic strains of mice who develop spontaneous osteoarthritis or obesity, or in mice who have a destabilized medial meniscus to predispose them to osteoarthritis (51).…”

Section: Discussionmentioning

confidence: 99%

Mercury Is Taken Up Selectively by Cells Involved in Joint, Bone, and Connective Tissue Disorders

Pamphlett

Jew

2019

Front. Med.

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Background: The causes of most arthropathies, osteoarthritis, and connective tissue disorders remain unknown, but exposure to toxic metals could play a part in their pathogenesis. Human exposure to mercury is common, so to determine whether mercury could be affecting joints, bones, and connective tissues we used a histochemical method to determine the cellular uptake of mercury in mice. Whole neonatal mice were examined since this allowed histological assessment of mercury in joint, bone, and connective tissue cells. Materials and Methods: Pregnant mice were exposed to a non-toxic dose of 0.5 mg/m 3 of mercury vapor for 4 h a day on gestational days 14–18. Neonates were sacrificed at postnatal day 1, fixed in formalin, and transverse blocks of the body were processed for paraffin embedding. Seven micrometer sections were stained for inorganic mercury using silver nitrate autometallography, either alone or combined with CD44 immunostaining to detect progenitor cells. Control neonates were not exposed to mercury during gestation. Results: Uptake of mercury was marked in synovial cells, articular chondrocytes, and periosteal and tracheal cartilage cells. Mercury was seen in fibroblasts in the dermis, aorta, esophagus and striated muscle, some of which were CD44-positive progenitor cells, and in the endothelial cells of small blood vessels. Mercury was also present in renal tubules and liver periportal cells. Conclusions: Mercury is taken up selectively by cells that are predominantly affected in rheumatoid arthritis and osteoarthritis. In addition, fibroblasts in several organs often involved in multisystem connective tissue disorders take up mercury. Mercury provokes the autoimmune, inflammatory, genetic, and epigenetic changes that have been described in a range of arthropathies and bone and connective tissue disorders. These findings support the hypothesis that mercury exposure could trigger some of these disorders, particularly in people with a genetic susceptibility to autoimmunity.

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“…Cd is an environmental pollutant that is dangerous to health, and according to Hutchinson (2015), smoking is the main source of Cd. The main studies about the effect of Cd on the osteoarticular system are related to osteomalacia, osteoporosis, rheumatoid arthritis (RA), and OA (Hutchinson, 2015; Joo et al, 2019; Kamiński et al, 2018; Reyes-Hinojosa et al, 2019). Studies in osteoblast cell lines indicate that Cd toxicity is related to its capacity of being absorbed and accumulating in the cells (Lévesque et al, 2008; Smith et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Cd can also cause peptide citrullination, a process that has been associated as part of RA development (Hutchinson, 2015). Joo et al (2019) demonstrated that RA patients have increased Cd levels (1.30 mg/L) in blood, associating it with RA risk.…”

Section: Introductionmentioning

confidence: 99%

Effect of cadmium on the viability on monolayer cultures of synoviocytes, chondrocytes, and Hoffa: A preliminary study

et al. 2020

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Osteoarthritis (OA) is the gradual loss of articular cartilage and involves several tissues, such as the synovial membrane, meniscus, ligaments, and adipose tissue known as Hoffa fat pad. There are largely unexplored factors that lead to OA development, such as the impact of exposure to heavy metals like cadmium (Cd) on the viability of cells in the knee joint tissue. The objective of this report was to identify the cell type with the highest susceptibility to Cd toxicity with respect to cell viability and death. Our findings showed that a concentration as low as 3 μM cadmium chloride for 12 h affects the viability of synovial cells, and a concentration of 10 μM affects Hoffa cells. Our results suggest that Cd can affect the viability of synovial and chondral cells primarily. In contrast, Hoffa cells were less susceptible, likely because Cd favors the production of pro-inflammatory cytokines before triggering their death as part of its damage mechanism at the articular level.

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Prevalence of rheumatoid arthritis in relation to serum cadmium concentrations: cross-sectional study using Korean National Health and Nutrition Examination Survey (KNHANES) data

Cited by 24 publications

References 47 publications

Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis

Zinc and Cadmium in the Aetiology and Pathogenesis of Osteoarthritis and Rheumatoid Arthritis

Mercury Is Taken Up Selectively by Cells Involved in Joint, Bone, and Connective Tissue Disorders

Effect of cadmium on the viability on monolayer cultures of synoviocytes, chondrocytes, and Hoffa: A preliminary study

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