GM1 Ganglioside Promotes Osteogenic Differentiation of Human Tendon Stem Cells.

Sonia Bergante,Michelle M Monasky,Carlo Pappone,Pasquale Creo,Federica Cirillo,Luigi Anastasia,Paola Rota,Marco Piccoli,Pietro Randelli,Andrea Ghiroldi,Alessandra Menon,Giuseppe Ciconte

doi:10.1155/2018/4706943

Abstract

Gangliosides, the sialic acid-conjugated glycosphingolipids present in the lipid rafts, have been recognized as important regulators of cell proliferation, migration, and apoptosis. Due to their peculiar localization in the cell membrane, they modulate the activity of several key cell receptors, and increasing evidence supports their involvement also in stem cell differentiation. In this context, herein we report the role played by the ganglioside GM1 in the osteogenic differentiation of human tendon stem cells (hTSCs). In particular, we found an increase of GM1 levels during osteogenesis that is instrumental for driving the process. In fact, supplementation of the ganglioside in the medium significantly increased the osteogenic differentiation capability of hTSCs. Mechanistically, we found that GM1 supplementation caused a reduction in the phosphorylation of the platelet-derived growth factor receptor-β (PDGFR-β), which is a known inhibitor of osteogenic commitment. These results were further corroborated by the observation that GM1 supplementation was able to revert the inhibitory effects on osteogenesis when the process was inhibited with exogenous PDGF.

Highlights

Injuries to the tendon-to-bone enthesis are common in the field of orthopedic medicine, and high failure rates are often associated with their repair [1]
To assess the ganglioside pattern distribution of human tendon stem cells (hTSCs), cells were metabolically radiolabeled with the sphingolipid precursor [3-3H]-sphingosine and quantitatively analyzed by HTPLC coupled with a radiochromatoscanner, as described in “Materials and Methods.”
Changes in ganglioside pattern were evaluated upon differentiation of hTSCs to either osteoblasts or adipocytes, as previously reported [4], by metabolic radiolabeling after 17 and 21 days of cell culturing in either osteogenic (O.D.) or adipogenic (A.D.) medium (Figure 1(a))

Summary

Introduction

Injuries to the tendon-to-bone enthesis are common in the field of orthopedic medicine, and high failure rates are often associated with their repair [1]. An open issue in the stem cell field is to perfect the differentiation strategies in order to drive the process toward a specific phenotype and to avoid undesired cell commitment or, even more detrimental, the uncontrolled proliferation of undifferentiated progenitor cells. In this context, we investigated the role of gangliosides, which are sialic acid-containing glycosphingolipids (GSLs) ubiquitously distributed in cell membranes [5], in the osteogenic differentiation of hTSCs. Numerous studies have confirmed that gangliosides and their expression levels are controlled during development [6] and are cell type-

Methods

Results

Conclusion