Sarcoglycans Role in Actin Cytoskeleton Dynamics and Cell Adhesion of Human Articular Chondrocytes: New Insights from siRNA-Mediated Gene Silencing.

Chondrocytes maintain cartilage integrity through coordinated regulation of extracellular matrix (ECM) synthesis and remodeling. These processes depend on ECM dynamic interactions, mediated by integrin-based focal adhesions and associated cytoskeletal components. While the roles of core adhesion proteins are well described, the involvement of sarcoglycans (SGs) remains unclear in chondrocytes. Drawing parallels from striated muscle, where the SG subcomplex stabilizes the sarcolemma, we hypothesized that SGs similarly integrate into chondrocyte adhesion complexes. This study investigated the SGs (α, β, γ, δ) expression with cytoskeletal and adhesion proteins, including actin and vinculin, in human chondrocytes cultured by immunofluorescence, qPCR, and siRNA-mediated silencing. All four SG isoforms were expressed in the cytoplasmic and membrane domains, with enrichment at focal adhesion sites. Double labeling revealed SG colocalization with F-actin stress fibers and vinculin, indicating integration into the core adhesion complex. Silencing of each SG resulted in disrupted actin stress fibers, diffuse vinculin distribution, reduced focal plaque number, and a change in cell morphology. These findings support the hypothesis that SGs regulate actin cytoskeletal dynamics and focal contact stabilization. Loss of SG function compromises chondrocyte shape and adhesion, highlighting the importance of these glycoproteins also in non-muscle cells.