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GM1 Ganglioside Promotes Osteogenic Differentiation of Human Tendon Stem Cells

机译:GM1神经节苷脂促进人肌腱干细胞成骨分化。

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摘要

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.
机译:神经节苷脂,存在于脂质筏中的唾液酸结合的糖鞘脂,已经被认为是细胞增殖,迁移和凋亡的重要调节剂。由于它们在细胞膜中的特殊定位,它们调节了几种关键细胞受体的活性,越来越多的证据支持它们也参与干细胞分化。在本文中,我们报道了神经节苷脂GM1在人肌腱干细胞(hTSCs)的成骨分化中所起的作用。特别是,我们发现在成骨过程中GM1水平升高,这对推动该过程至关重要。实际上,在培养基中补充神经节苷脂显着提高了hTSC的成骨分化能力。从机理上讲,我们发现补充GM1导致血小板衍生生长因子受体-β(PDGFR-β)的磷酸化降低,而后者是已知的成骨作用抑制剂。当外源性PDGF抑制GM1时,补充GM1能够恢复对成骨的抑制作用,从而进一步证实了这些结果。

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