High glucose regulates cyclin D1/E of human mesenchymal stem cells through TGF-β1expression via Ca2+/PKC/MAPKs and PI3K/Akt/mTOR signal pathways

Human mesenchymal stem cells (MSCs) are now widely adopted in regenerative medicine. However, many questions on the role of different signaling pathways in the regulation of stem cell (SC) functional activity within the organism remain unaswered. In damaged regions the level of cell death increases and DNA fragments from dead cells (cell-free DNA, cfDNA) are accumulated in blood. We showed that in adipose-derived MSCs exposed in vitro to cfDNA fragments the transcription level increased (the total amount of cellular RNA and the rRNA amount rose). GC-rich CfDNA fragments (GC-DNA) activated the TLR9-dependent signal pathway: the expression of TLR9 and of TLR9-signaling pathway adapter - MyD88 - was up-regulated. AT-rich DNA fragments did not increase the TLR9 expression, though, the MyD88 expression level rose. So we suggest that AT-DNA acts via some other receptors that nevertheless activate MyD88-dependent signalling in MSCs. We also showed that cfDNA fragments decreased the activity of caspase, an apoptotic enzyme. So, cfDNA can significantly influence the functional activity of MSC by activating TLR9- and MyD88-dependent signal pathways and lowering the apoptosis level.

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Low-Intensity Ultrasound Upregulates the Expression of Cyclin-D1 and Promotes Cellular Proliferation in Human Mesenchymal Stem Cells

Biotechnology Journal ◽

10.1002/biot.201700382 ◽

2018 ◽

Vol 13 (4) ◽

pp. 1700382 ◽

Cited By ~ 7

Author(s):

Gaurav Budhiraja ◽

Neety Sahu ◽

Anuradha Subramanian

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cyclin D1 ◽

Cellular Proliferation ◽

Human Mesenchymal Stem Cells ◽

Low Intensity ◽

Low Intensity Ultrasound

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Phosphatidylserine enhances osteogenic differentiation in human mesenchymal stem cells via ERK signal pathways

Materials Science and Engineering C ◽

10.1016/j.msec.2013.01.005 ◽

2013 ◽

Vol 33 (3) ◽

pp. 1783-1788 ◽

Cited By ~ 14

Author(s):

Caixia Xu ◽

Zebin Zheng ◽

LiMing Fang ◽

Naru Zhao ◽

Zihong Lin ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Human Mesenchymal Stem Cells ◽

Signal Pathways

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New Insights into Osteogenic and Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells and Their Potential Clinical Applications for Bone Regeneration in Pediatric Orthopaedics

Stem Cells International ◽

10.1155/2013/312501 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 44

Author(s):

Nicola Giuliani ◽

Gina Lisignoli ◽

Marina Magnani ◽

Costantina Racano ◽

Marina Bolzoni ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Transcription Factor ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Chondrogenic Differentiation ◽

Adult Stem Cells ◽

Molecular Mechanisms ◽

Human Mesenchymal Stem Cells ◽

Signal Pathways

Human mesenchymal stem cells (hMSCs) are pluripotent adult stem cells capable of being differentiated into osteoblasts, adipocytes, and chondrocytes. The osteogenic differentiation of hMSCs is regulated either by systemic hormones or by local growth factors able to induce specific intracellular signal pathways that modify the expression and activity of several transcription factors. Runt-related transcription factor 2 (Runx2) and Wnt signaling-related molecules are the major factors critically involved in the osteogenic differentiation process by hMSCs, and SRY-related high-mobility-group (HMG) box transcription factor 9 (SOX9) is involved in the chondrogenic one. hMSCs have generated a great interest in the field of regenerative medicine, particularly in bone regeneration. In this paper, we focused our attention on the molecular mechanisms involved in osteogenic and chondrogenic differentiation of hMSC, and the potential clinical use of hMSCs in osteoarticular pediatric disease characterized by fracture nonunion and pseudarthrosis.

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