Ganglioside GM3 Up-Regulate Chondrogenic Differentiation by Transform Growth Factor Receptors

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.

Fatty sweet symphony: Decoding distinct ganglioside patterns of native and differentiated mesenchymal stem cells by a novel glycolipidomics profiling strategy

“…Hence, we propose several GM3 ganglioside (molecular) species as potential markers for adipogenic differentiation ( Figure 7 ). Regarding chondrogenic differentiation, our study does not confirm former results(Ryu et al, 2020). Instead of increased expression of GM3 and GD3, we found ganglioside classes GM4 and GT3 significantly upregulated in the chondrogenic lineage compared to native MSCs.…”

Alterations of Glycosphingolipid Glycans and Chondrogenic Markers during Differentiation of Human Induced Pluripotent Stem Cells into Chondrocytes

“…After chondrogenic differentiation of both BMSCs and iPS-MSC like cells, the expression of GM3 increased temporarily. Ryu et al reported that GM3 and GD3 were expressed after chondrogenic differentiation and GM3 enhanced TGF-β signaling via SMAD 2/3 [32]. These results might suggest that BMSCs and iPS-MSCs differentiated into chondrocytes.…”

Gangliosides and Their Role in Multilineage Differentiation of Mesenchymal Stem Cells

“…On the other hand, after the chondrogenic differentiation of BM-MSCs, the expression of GM3 temporarily increases. Ryu et al reported that GM3 and GD3 are expressed after the chondrogenic differentiation and GM3 enhanced transforming growth factor-beta (TGF-β) signaling via SMAD 2/3 [ 37 ]. However, GM3 levels significantly decreased, whereas GM1, GD3, and GD1a levels increased during further differentiation into chondrocytes [ 87 ].…”

“…GGs have important biological characteristics and functions [ 34 ], including regulation of cell proliferation, adhesion, migration, apoptosis, cell-cell interactions, cell differentiation [ 35 , 36 , 37 ], and interaction with proteins [ 38 , 39 ].…”