Centofanti Antonio, Runci Anastasi Michele, Nicita Fabiana, Labellarte Davide, Scuruchi Michele, Pantano Alice, Freni Josè, Favaloro Angelo, Vermiglio Giovanna
Department of Biomedical, Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy.
Department of Maxillo-Facial Surgery, University of Sapienza, 00161 Rome, Italy.
Int J Mol Sci. 2025 Jun 15;26(12):5732. doi: 10.3390/ijms26125732.
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.
软骨细胞通过对细胞外基质（ECM）合成与重塑的协调调控来维持软骨的完整性。这些过程依赖于由整合素介导的粘着斑及相关细胞骨架成分所介导的ECM动态相互作用。虽然核心粘附蛋白的作用已得到充分描述，但肌聚糖（SGs）在软骨细胞中的作用仍不清楚。借鉴横纹肌中SG亚复合物稳定肌膜的情况，我们推测SGs同样整合到软骨细胞粘附复合物中。本研究通过免疫荧光、qPCR和siRNA介导的沉默技术，研究了人软骨细胞中SGs（α、β、γ、δ）与细胞骨架和粘附蛋白（包括肌动蛋白和纽蛋白）的表达情况。所有四种SG亚型均在细胞质和膜结构域中表达，并在粘着斑部位富集。双重标记显示SG与F-肌动蛋白应力纤维和纽蛋白共定位，表明其整合到核心粘附复合物中。每种SG的沉默都会导致肌动蛋白应力纤维破坏、纽蛋白分布弥散、粘着斑数量减少以及细胞形态改变。这些发现支持了SGs调节肌动蛋白细胞骨架动力学和粘着斑稳定的假说。SG功能丧失会损害软骨细胞的形状和粘附，突出了这些糖蛋白在非肌肉细胞中的重要性。
