Caveolin‐1 regulates neural differentiation of rat bone mesenchymal stem cells into neurons by modulating Notch signaling

Abstract

Bone marrow mesenchymal stem cells (MSCs) are known to differentiate into neurons in vitro. However, the mechanism underlying MSC differentiation remains controversial. A recent analysis has shown that Notch signaling is involved in regulating the differentiation of MSCs. This study examines the potential mechanism of the differentiation of MSCs into neurons, and it considers the role of caveolin-1 in this process. We investigated neuron differentiation and Notch signaling by detecting the expression levels of microtubule-associated protein 2 (MAP-2), Neuron-specific Enolase (NSE), Notch-1, Notch intracellular domain (NICD) and hairy enhancer of split 5 (Hes5). We found that by down-regulating caveolin-1 during induction, MSCs were prone to neural differentiation and expressed high levels of neuronal markers. Meanwhile, the expression levels of Notch-1, NICD and Hes5 decreased. Our results indicate that down-regulation of caveolin-1 promotes the neuronal differentiation of MSCs by modulating the Notch signaling pathway.

Caveolin-1 Plays an Important Role in the Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Cardiomyocytes

“…These results suggest that caveolin-1 negatively regulates the cardiomyocyte differentiation of BMSCs. Our results agree with a recent study that the downregulation of caveolin-1 promotes the differentiation of rat BMSCs into neurons [28]. Our findings also agree with studies in other cell types that show that caveolin-1 negatively regulates cell differentiation [21,24], and observations of increased populations of cells expressing stem cell markers in the gut, mammary gland and brain of the caveolin-1 knockout mouse [47,48,49].…”

“…Our result agrees with previous reports that caveolin-1 is highly expressed in terminally differentiated cells of mesenchymal lineages [24,28]. This may reflect negative feedback, where caveolin-1 expression increases as cells differentiate to stabilize the phenotype and prevent continued growth and differentiation.…”

“…It has been demonstrated that caveolin-1 expression increases during osteogenic differentiation of human BMSCs and the knockdown of caveolin-1 expression enhances this differentiation [24]. Wang et al [28 ]reported that downregulation of caveolin-1 promotes the neuronal differentiation of rat BMSCs by modulating the Notch signaling pathway. These reports indicate that caveolin-1 plays a role in the regulation of MSC differentiation.…”

Mash1-dependent Notch Signaling Pathway Regulates GABAergic Neuron-Like Differentiation from Bone Marrow-Derived Mesenchymal Stem Cells

“…Nonetheless, a method that greatly enhances the production of GABAergic neuron-like cells from BMSCs is yet to be discovered. While it is well known that the Notch signaling is an evolutionarily conserved system that regulates proliferation and differentiation of BMSCs [29, 30], the regulatory role of Notch signaling in the differentiation of BMSCs into GABAergic neuron-like cells has not been examined.…”

Genetic Engineering of Mesenchymal Stem Cells for Regenerative Medicine

“…Caveolin-1 was found to interact with the membrane receptor Notch-1, which, in turn, is involved in neuronal [237] and astroglial differentiation of NSCs [238]. In the case of BM-MSCs, the downregulation of the Caveolin-1 gene expression was achieved with siRNA engineering, and modified cells were more sensitive for neuronal differentiation, which was affirmed by the expression of several neural-specific markers [239].…”