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.
Background and Objectives: Deposits of monosodium urate (MSU) crystals due to increased levels of uric acid (UA) have been associated with bone formation and erosion, mainly in patients with chronic gout. The synovial membrane (SM) comprises several types of cells, including mesenchymal stem cells (SM-MSCs); however, it is unknown whether UA and MSU induce osteogenesis through SM-MSCs. Materials and Methods: Cultures of SM were immunotyped with CD44, CD69, CD90, CD166, CD105, CD34, and CD45 to identify MSCs. CD90+ cells were isolated by immunomagnetic separation (MACS), colony-forming units (CFU) were identified, and the cells were exposed to UA (3, 6.8, and 9 mg/dL) and MSU crystals (1, 5, and 10 μg/mL) for 3 weeks, and cellular morphological changes were evaluated. IL-1β and IL-6 were determined by ELISA, mineralization was assessed by alizarin red, and the expression of Runx2 was assessed by Western blot. Results: Cells derived from SM and after immunomagnetic separation were positive for CD90 (53 ± 8%) and CD105 (52 ± 18%) antigens, with 53 ± 5 CFU identified. Long-term exposure to SM-MSCs by UA and MSU crystals did not cause morphological damage or affect cell viability, nor were indicators of inflammation detected. Mineralization was observed at doses of 6.8 mg/dL UA and 5 μg/mL MSU crystals; however, the differences were not significant with respect to the control. The highest dose of MSU crystals (10 μg/mL) induced significant Runx2 expression with respect to the control (1.4 times greater) and SM-MSCs cultured in the osteogenic medium. Conclusions: MSU crystals may modulate osteogenic differentiation of SM-MSCs through an increase in Runx2.
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