Impact of Cadmium Mediated by Tobacco Use in Musculoskeletal Diseases.

Tobacco use has a negative impact on health due to its relationship with the development of high-mortality diseases, such as pulmonary cancer. However, the effect of cadmium (Cd), present in tobacco smoke, on the development of joint diseases has been scarcely studied. The objective of this review is to discuss the evidence regarding the mechanisms by which Cd exposure, through tobacco smoke, may lead to the development of osteoarthritis (OA), osteoporosis (OP), and rheumatoid arthritis (RA). There's evidence suggesting a string association between moderate to severe OA development and tobacco use, and that a higher blood concentration of Cd can trigger oxidative stress (OS) and inflammation, favoring cartilage loss. At the bone level, the Cd that is inhaled through tobacco smoke affects bone mineral density, resulting in OP mediated by a decrease in the antioxidant enzymes, which favors the bone resorption process. In RA, tobacco use promotes the citrullination process through Cd exposure and increases OS and inflammation. Understanding how tobacco use can increase the damage at the articular level mediated by a toxic metal, i.e., Cd, is important. Finally, we propose prevention, control, and treatment strategies for frequently disabling diseases, such as OA, OP, and RA to reduce its prevalence in the population.

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

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.

Effect of cadmium on the concentration of essential metals in a human chondrocyte micromass culture.

BACKGROUND: An essential element imbalance in the joint might favor gradual degeneration of the articular cartilage. It has been reported that cadmium (Cd) plays an antagonistic role with regards to the presence of essential elements, such as zinc (Zn), iron (Fe), and manganese (Mn), which may favor the development of disabling diseases, like osteoarthritis (OA) and osteoporosis. METHODS: 3D cultures of human chondrocytes were phenotyped with the Western blot technique and structurally evaluated with histological staining. The samples were exposed to 1, 5, and 10 µM of CdCl2 for 12 h, with a non-exposed culture as control. The concentration of Cd, Fe, Mn, Zn, chromium (Cr), and nickel (Ni) was quantified through plasma mass spectrometry (ICP-MS). The data were analyzed with a Kruskal Wallis test, a Kendall's Tau test and Spearman's correlation coefficient with the Stata program, version 14. RESULTS: Our results suggest that Cd exposure affects the structure of micromass cultures and plays an antagonistic role on the concentration of essential metals, such as Zn, Ni, Fe, Mn, and Cr. CONCLUSION: Cd exposure may be a risk factor for developing joint diseases like OA, as it can interfere with cartilage absorption of other essential elements that maintain cartilage homeostasis.

Toxicity of cadmium in musculoskeletal diseases.

Epidemiological studies have reported that exposure to toxic metals like cadmium (Cd) may promote the development of musculoskeletal diseases, such as osteoporosis, rheumatoid arthritis (RA), and osteoarthritis (OA), among others. The objective of this review is to summarize the molecular mechanisms of inflammation and oxidative stress activated by Cd at the bone level, particularly in osteoporosis, RA, and OA. Cadmium can increase bone resorption, affect the activity of osteoclasts and calcium (Ca) absorption, and impair kidney function, which favors the development of osteoporosis. In the case of RA, Cd interferes with the activity of antioxidant proteins, like superoxide dismutase (SOD) and catalase (CAT). It also promotes an inflammatory state, inducing the process of citrullination, which affects the proteins of immune response. On the other hand, accumulation of Cd in the tissues and blood of smokers has been related to the development of some musculoskeletal diseases. Therefore, knowing the negative impact of Cd toxicity at the articular level can help understand the damage mechanisms it produces, leading to the development of such diseases.

Hypoxia-Inducible Factors (HIFs) in the articular cartilage: a systematic review.

Osteoarthritis (OA) is the most common joint disease, and in recent years has become a major public health problem. The hallmark of OA is cartilage destruction with local commitment of subchondral bone and the synovial membrane. Hypoxia-inducible factors (HIFs) are transcriptional factors and key regulators of the cellular response to hypoxia. To date, three members of the human HIF-α protein family have been described: HIF-1α, HIF-2α, and HIF-3α. HIF-1α plays an essential role in the articular cartilage (a hypoxic tissue), as it has a protective effect in the maintenance of the articular cartilage matrix, HIF-2α has a harmful effect on the articular cartilage matrix, and HIF-3α acts as a negative regulator of HIF-1α and HIF-2α. Due to the recent growing interest in the role of HIFs in rheumatic diseases, we focused this review on the potential role of these key regulators in articular cartilage maintenance as the central axis in OA development.

The antioxidant activity of soursop decreases the expression of a member of the NADPH oxidase family.

Cellular oxidative stress produced by an increase in free radicals is one of the factors that promote the development of chronic degenerative diseases; therefore, consuming natural antioxidants helps minimize their negative effects. This study evaluated the cytotoxicity of the soursop extract (Annona muricata), its cytoprotective capacity against oxidative stress induced by hydrogen peroxide, the inhibitory potential of reactive oxygen species (ROS), the molecular mechanism of its antioxidant action, and its capacity to repair cellular damage in the fibroblast cell line. The soursop extract proved not to be cytotoxic in fibroblast cultures and showed cytoprotective capacity against hydrogen peroxide-induced stress; in cell culture it reduced the generation of ROS significantly by inhibiting a sub-unit of the NADPH oxidase enzyme (p47phox). The soursop extract can prevent damage caused by cellular oxidants.