Abstract
Mesenchymal stem cells, also known as multipotent stromal progenitor cells, can differentiate into cells of mesodermal lineage. Gangliosides are sialic acid-conjugated glycosphingolipids that are believed to regulate cell differentiation and several signaling molecules. These molecules are localized in glycosphingolipid-enriched microdomains on the cell surface and are regulated by glycosphingolipid composition. Transforming growth factor-beta (TGF-β) signaling plays a critical role in chondrogenic differentiation. However, the role of gangliosides in chondrogenesis is not understood. In this study, the relationship between the ganglioside GM3 and TGF-β activation, during chondrogenic differentiation, was investigated using an aggregate culture of human synovial membrane-derived mesenchymal stem cells. We showed that the gangliosides GM3 and GD3 were expressed after the chondrogenic differentiation of hSMSC aggregates. To test whether GM3 affected the chondrogenic differentiation of hSMSC aggregates, we used GM3 treatment during chondrogenic differentiation. The results showed that the group treated with 5 μM GM3 had higher expression of chondrogenic specific markers, increased toluidine blue, and safranin O staining, and increased accumulation of glycosaminoglycans compared with the untreated group. Furthermore, GM3 treatment enhanced TGF-β signaling via SMAD 2/3 during the chondrogenic differentiation of hSMSC aggregates. Taken together, our results suggested that GM3 may be useful in developing therapeutic agents for cell-based articular cartilage regeneration in articular cartilage disease.
Highlights
Mesenchymal stem cells (MSCs), referred to as multipotent stromal progenitor cells, can be differentiated into cells of mesodermal lineage, such as chondrocytes, osteoblasts, and adipocytes, making them an interesting candidate in regenerative medicine [1,2]
We investigated whether human synovium-derived mesenchymal stem cells (SMSCs) could differentiate into chondrocyte and the role of the ganglioside, GM3, in chondrogenic differentiation of hSMSCs
Characterized hSMSCs were differentiated into chondrocytes using the aggregation culture system and showed chondrocyte marker expression upon differentiation (Supplementary Figure S2)
Summary
Mesenchymal stem cells (MSCs), referred to as multipotent stromal progenitor cells, can be differentiated into cells of mesodermal lineage, such as chondrocytes, osteoblasts, and adipocytes, making them an interesting candidate in regenerative medicine [1,2]. Numerous studies have confirmed that the pattern and level of ganglioside expression are subject to developmental and cell-type specific regulation [12,13]. Results from our recent studies have suggested that the expression of gangliosides is closely related to the differentiation of stem cells in vitro [14,15,16]. GM3 has been shown to regulate tyrosine phosphorylation of growth factor receptors [17,18,19]. The TGF-β related signal transduction includes initial internalization via serine/threonine phosphorylation of TGF-β receptor (TGF-βR) after pairing of TGF-βR1 and TGF-βR2 on the cell surface [24]. We investigated whether human SMSCs (hSMSCs) could differentiate into chondrocyte and the role of the ganglioside, GM3, in chondrogenic differentiation of hSMSCs
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