UGC de Reumatología, Hospital Clínico San Carlos, IdISSC, 28040 Madrid, Spain.
Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Cells. 2024 May 16;13(10):852. doi: 10.3390/cells13100852.
In this study of the alterations of Glypicans 1 to 6 (GPCs) and Notum in plasma, bone marrow mesenchymal stromal cells (BM-MSCs) and osteoblasts in Osteoarthritis (OA), the levels of GPCs and Notum in the plasma of 25 patients and 24 healthy subjects were measured. In addition, BM-MSCs from eight OA patients and eight healthy donors were cultured over a period of 21 days using both a culture medium and an osteogenic medium. Protein and gene expression levels of GPCs and Notum were determined using ELISA and qPCR at 0, 7, 14 and 21 days. GPC5 and Notum levels decreased in the plasma of OA patients, while the BM-MSCs of OA patients showed downexpression of GPC6 and upregulation of Notum. A decrease in GPC5 and Notum proteins and an increase in GPC3 were found. During osteogenic differentiation, elevated GPCs 2, 4, 5, 6 and Notum mRNA levels and decreased GPC3 were observed in patients with OA. Furthermore, the protein levels of GPC2, GPC5 and Notum decreased, while the levels of GPC3 increased. Glypicans and Notum were altered in BM-MSCs and during osteogenic differentiation from patients with OA. The alterations found point to GPC5 and Notum as new candidate biomarkers of OA pathology.
在这项关于软骨蛋白聚糖 1 到 6（GPCs）和 Notum 在血浆、骨髓间充质基质细胞（BM-MSCs）和骨关节炎（OA）成骨细胞中的改变的研究中，测量了 25 名患者和 24 名健康受试者血浆中的 GPCs 和 Notum 水平。此外，培养了 8 名 OA 患者和 8 名健康供体的 BM-MSCs，使用培养基于成骨培养基培养 21 天。在第 0、7、14 和 21 天，使用 ELISA 和 qPCR 测定 GPCs 和 Notum 的蛋白和基因表达水平。OA 患者的血浆中 GPC5 和 Notum 水平降低，而 OA 患者的 BM-MSCs 中 GPC6 的表达下调，Notum 的表达上调。发现 GPC5 和 Notum 蛋白减少，GPC3 增加。在成骨分化过程中，OA 患者的 GPCs 2、4、5、6 和 Notum mRNA 水平升高，GPC3 减少。此外，GPC2、GPC5 和 Notum 的蛋白水平降低，而 GPC3 的水平升高。OA 患者的 BM-MSCs 中以及成骨分化过程中，Glypicans 和 Notum 发生改变。这些变化表明 GPC5 和 Notum 是 OA 病理的新候选生物标志物。
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