Abstract
Extracellular calcium ion concentration levels increase in human osteoarthritic (OA) joints and contribute to OA pathogenesis. Given the fact that OA is a mechanical problem, the effect of the extracellular calcium level ([Ca2+]) on the mechanical behavior of primary human OA chondrocytes remains to be elucidated. Here, we measured the elastic modulus and cell–ECM adhesion forces of human primary chondrocytes with atomic force microscopy (AFM) at different extracellular calcium ion concentration ([Ca2+]) levels. With the [Ca2+] level increasing from the normal baseline level, the elastic modulus of chondrocytes showed a trend of an increase and a subsequent decrease at the level of [Ca2+], reaching 2.75 mM. The maximum increment of the elastic modulus of chondrocytes is a 37% increase at the peak point. The maximum unbinding force of cell-ECM adhesion increased by up to 72% at the peak point relative to the baseline level. qPCR and immunofluorescence also indicated that dose-dependent changes in the expression of myosin and integrin β1 due to the elevated [Ca2+] may be responsible for the variations in cell stiffness and cell-ECM adhesion. Scratch assay showed that the chondrocyte migration ability was modulated by cell stiffness and cell-ECM adhesion: as chondrocyte’s elastic modulus and cell-ECM adhesion force increased, the migration speed of chondrocytes decreased. Taken together, our results showed that [Ca2+] could regulate chondrocytes stiffness and cell-ECM adhesion, and consequently, influence cell migration, which is critical in cartilage repair.
Highlights
Introduction iationsOsteoarthritis (OA) is a common joint disorder and a leading cause of physical disability; one of its characteristics is articular cartilage degeneration [1]
Extracellular calcium ions regulate osteoclast’s integrin expression and change the adhesion, influence the cell’s migration [26]. These results suggest that extracellular calcium ions may regulate chondrocyte adhesion
We demonstrated the critical role of myosin and integrin in chondrocyte mechanics and migration
Summary
Osteoarthritis (OA) is a common joint disorder and a leading cause of physical disability; one of its characteristics is articular cartilage degeneration [1]. There is no effective way to cure OA at present, despite its negative impacts on patients’ life quality. Abnormal extracellular calcium ion concentration was reported in osteoarthritic cartilage and in severe OA cases where calcium crystals were found in the joint fluid and hyaline articular cartilage of patients [4,5,6]. Extracellular calcium ([Ca2+ ]) may play an important role in OA pathogenesis [7]. In the synovial fluid, the [Ca2+ ] of OA patients was significantly higher than that of the healthy people [8,9]
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