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

Abstract

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.

An Extremely Stable Interprotein Tetrahedral Hg(Cys)4 Core Forms in the Zinc Hook Domain of Rad50 Protein at Physiological pH

“…[ 69 , 70 , 71 , 72 , 73 , 74 , 75 ] Hg II ions were also found to inhibit the DNA binding activity of the Cys 2 His 2 zinc finger protein transcription factor III A and Sp1 in vitro, although no information on the Hg II coordination was provided. [ 76 , 77 , 78 ] Importantly, the affinity of Hg II towards Rad50 hook models examined in this study was found, not surprisingly, to be significantly higher than the affinity towards Zn II . Taken together, the zinc hook domain could serve as an excellent target for Hg II binding and the resulting genotoxic activity.…”

“…In fact, the accumulation of mercury inside the cell nucleus and its association with non‐histone proteins of chromatin after mercury exposure in mice, rats, or in isolated cells, was detected years ago [69–75] . Hg II ions were also found to inhibit the DNA binding activity of the Cys 2 His 2 zinc finger protein transcription factor III A and Sp1 in vitro, although no information on the Hg II coordination was provided [76–78] . Importantly, the affinity of Hg II towards Rad50 hook models examined in this study was found, not surprisingly, to be significantly higher than the affinity towards Zn II .…”

Dental Amalgams and the Incidence Rate of Arthritis among American Adults

“…Investigators recently examined Hg distribution following mice exposed to Hg vapor to determine whether it localize in areas known to be impacted in arthritis. 13 These investigators reported that Hg was found to localize in the synovial cells and articular chondrocytes. These cell types are known to be affected in persons suffering from arthritis.…”

Concentration of Selected Macronutrients and Toxic Elements in the Blood in Relation to Pain Severity and Hydrogen Magnetic Resonance Spectroscopy in People with Osteoarthritis of the Spine

“…In addition, Hg is taken up by fibroblasts in several organs, often involved in multi-system connective tissue disorders. Hg induces autoimmune, inflammatory, genetic and epigenetic changes that have been described in a number of arthropathies and bone and connective tissue diseases [ 40 ]. In our study, both in the group of people with a degenerative disease of the spine and in the control group, there were no people whose Hg concentration exceeded the maximum permissible levels.…”