scholarly journals Hypoxia Inducible Factor-1αRegulates the Migration of Bone Marrow Mesenchymal Stem Cells via Integrinα4

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Jong Ho Choi ◽  
Yun Bin Lee ◽  
Jieun Jung ◽  
Seong Gyu Hwang ◽  
IL-Hoan Oh ◽  
...  

Although hypoxic environments have been known to regulate the migratory ability of bone marrow-derived mesenchymal stem cells (BM-MSCs), which is a critical factor for maximizing the therapeutic effect, the underlying mechanisms remain unclear. Therefore, we aimed to confirm the effect of hypoxia-inducible factor-1α(HIF-1α) on the migration of BM-MSCs and to analyze the interaction between HIF-1αand integrin-mediated signals. Hypoxia-activated HIF-1αsignificantly increased BM-MSC migration. The expression of integrinα4was decreased in BM-MSCs by increased HIF-1αunder hypoxia, whereas the expression of Rho-associated kinase 1 (ROCK1) and Rac1/2/3 was increased. After downregulation of HIF-1αby YC-1, which is an inhibitor of HIF-1α, BM-MSC migration was decreased via upregulation of integrinα4and downregulation of ROCK1 and Rac1/2/3. Knockdown of integrinα4by integrinα4siRNA (siITGA4) treatment increased BM-MSC migration by upregulation of ROCK1, Rac1/2/3, and matrix metalloproteinase-2 regardless of oxygen tension. Moreover, siITGA4 treatment increased HIF-1αexpression and augmented the translocation of HIF-1αinto the nucleus under hypoxia. Taken together, the alternative expression of HIF-1αinduced by microenvironment factors, such as hypoxia and integrinα4, may regulate the migration of BM-MSCs. These findings may provide insights to the underlying mechanisms of BM-MSC migration for successful stem cell-based therapy.

2019 ◽  
Vol 47 (7) ◽  
pp. 3261-3270
Author(s):  
Cheng Wang ◽  
Qiaohui Liu ◽  
Xiaoyuan Ma ◽  
Guofeng Dai

Objective To measure the inductive effect of kartogenin on matrix metalloproteinase-2 levels during the differentiation of human bone marrow mesenchymal stem cells (hMSCs) into chondrocytes in vitro. Methods In vitro cultured bone marrow hMSCs were grown to the logarithmic phase and then divided into three groups: control group (0 µM kartogenin), 1 µM kartogenin group and 10 µM kartogenin group. After 72 h of culture, cell proliferation and differentiation were observed microscopically. Matrix metalloproteinase-2 (MMP-2) in the cell supernatant and type II collagen levels in the cells were detected by enzyme linked immunosorbent assay and immunofluorescence staining, respectively. Results Kartogenin induced the proliferation and differentiation of hMSCs. With the increase of kartogenin concentration, the level of type II collagen was increased, while the level of MMP-2 decreased. Conclusion These findings indicate that kartogenin can induce hMSCs to differentiate into chondrocytes, and with the increase of kartogenin concentration, degeneration of the cartilage extracellular matrix may be inhibited.


2018 ◽  
Vol 8 (1) ◽  
pp. 23 ◽  
Author(s):  
May-Jywan Tsai ◽  
Dann-Ying Liou ◽  
Yan-Ru Lin ◽  
Ching-Feng Weng ◽  
Ming-Chao Huang ◽  
...  

Spinal cord injury (SCI) is a devastating neurological condition and might even result in death. However, current treatments are not sufficient to repair such damage. Bone marrow mesenchymal stem cells (BM-MSC) are ideal transplantable cells which have been shown to modulate the injury cascade of SCI mostly through paracrine effects. The present study investigates whether systemic administration of conditioned medium from MSCs (MSCcm) has the potential to be efficacious as an alternative to cell-based therapy for SCI. In neuron-glial cultures, MSC coculture effectively promoted neuronal connection and reduced oxygen glucose deprivation-induced cell damage. The protection was elicited even if neuron-glial culture was used to expose MSCcm, suggesting the effects possibly from released fractions of MSC. In vivo, intravenous administration of MSCcm to SCI rats significantly improved behavioral recovery from spinal cord injury, and there were increased densities of axons in the lesion site of MSCcm-treated rats compared to SCI rats. At early days postinjury, MSCcm treatment upregulated the protein levels of Olig 2 and HSP70 and also increased autophage-related proteins in the injured spinal cords. Together, these findings suggest that MSCcm treatment promotes spinal cord repair and functional recovery, possibly via activation of autophagy and enhancement of survival-related proteins.


2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Wei Wu ◽  
Ling Zhang ◽  
Min Zhang ◽  
Li-Jin Zhu ◽  
Hai-Ling Xia ◽  
...  

Benzene is metabolized to hydroquinone in liver and subsequently transported to bone marrow for further oxidization to 1,4-benzoquinone (1,4-BQ), which may be related to the leukemia and other blood disorders. In the present study, we investigated the proteome profiles of human primary bone marrow mesenchymal stem cells (hBM-MSCs) treated by 1,4-BQ. We identified 32 proteins that were differentially expressed. Two of them, HSP27 and Vimentin, were verified at both mRNA and protein levels and their cellular localization was examined by immunofluorescence. We also found increased mRNA level of RAP1GDS1, a critical factor of metabolism that has been identified as a fusion partner in various hematopoietic malignancies. Therefore, these differentially expressed proteins can play important roles in benzene-mediated hematoxicity.


2013 ◽  
Author(s):  
Melo Ocarino Natalia de ◽  
Silvia Silva Santos ◽  
Lorena Rocha ◽  
Juneo Freitas ◽  
Reis Amanda Maria Sena ◽  
...  

2014 ◽  
Author(s):  
Reis Amanda Maria Sena ◽  
Freitas Silva Juneo de ◽  
Silvia Silva Santos ◽  
Rogeria Serakides ◽  
Melo Ocarino Natalia de

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