scholarly journals IL-1β-mediated TGFβ/SMAD signaling pathway inactivation impaired ex vivo osteogenic activity of human bone marrow-derived stromal cells

2021 ◽  
Vol 35 (1) ◽  
pp. 1177-1189
Author(s):  
Amer Mahmood* ◽  
Mona Elsafadi* ◽  
Muthurangan Manikandan ◽  
Musaad Alfayez
Author(s):  
Lingli Zhang ◽  
Yu Yuan ◽  
Wei Wu ◽  
Zhongguang Sun ◽  
Le Lei ◽  
...  

As a type of multipotential cells, bone marrow mesenchymal stromal cells (BMMSCs) can differentiate into chondrocytes, osteoblasts, and adipocytes under different loading condition or specific microenvironment. Previous studies have shown that BMMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. The appropriate physical activity and exercise could help attenuate bone loss, effectively stimulate bone formation, increase bone mineral density (BMD), prevent the progression of osteoporosis, and reduce the risk of bone fractures. Bone morphogenetic protein (BMP) is originally discovered as a protein with heterotopic bone-inducing activity in the bone matrix that exerts a critical role in multiple stages of bone metabolism. In the present study, the medium-intensity treadmill exercise enhanced bone formation and increased osteocalcin (OCN) and osteopontin (OPN) mRNA expression as well as activation of the BMP-Smad signaling pathway in vivo. In order to investigate the effect of a BMP-Smad signaling pathway, we injected mice with activated enzyme inhibitors (LDN-193189HCL) and subjected the mice to treadmill exercise intervention. LDN-193189HCL attenuated the BMD and bone mass mediated by medium-intensity exercise and BMP-Smad signaling pathway.


Cytotherapy ◽  
2013 ◽  
Vol 15 (8) ◽  
pp. 920-929 ◽  
Author(s):  
Martina Bernardi ◽  
Elena Albiero ◽  
Alberta Alghisi ◽  
Katia Chieregato ◽  
Chiara Lievore ◽  
...  

2000 ◽  
Vol 28 (6) ◽  
pp. 707-715 ◽  
Author(s):  
Andrea Banfi ◽  
Anita Muraglia ◽  
Beatrice Dozin ◽  
Maddalena Mastrogiacomo ◽  
Ranieri Cancedda ◽  
...  

2019 ◽  
Vol 71 (2) ◽  
pp. 201-208
Author(s):  
Darija Loncaric ◽  
Biljana Stankovic ◽  
Amani Ghousein ◽  
Misa Vreca ◽  
Vesna Spasovski ◽  
...  

A major limitation in the development of efficient clinical protocols for mesenchymal stromal cell (MStroC)-based tissue regeneration therapy is the low retention and survival of MStroC in injured tissue after therapeutic administration. Low oxygen concentration preconditioning (LOP) during ex vivo cultivation of MStroC, as a method for mimicking oxygenation in their physiological microenvironment, has been shown to be beneficial in clinical trials using MStroC. Introducing hypoxia-mimicking molecules into MStroC during cultivation could be an advantageous LOP strategy. MicroRNA (miRNA) drugs are good candidates for this approach. Analysis of the expression of miRNA-210 in human bone marrow-derived MStroC in conditions of acute and extended hypoxia (24 to 72 h) was performed using RT-qPCR methodology. HIF-1? and HIF-2? gene knockdown cell lines were generated using lentiviral transduction of short hairpin RNA (shRNA) in order to examine whether miRNA-210 expression is regulated by transcription factor HIF-1 and/or HIF-2. We detected a significant increase in miRNA-210 expression in hypoxic conditions at time points of 24, 48 and 72 h (p<0.05). Knocking down of HIF-1? and HIF-2? genes indicated involvement of both transcription factors in the elevation of miRNA-210 expression. These results point to miRNA-210 as a good candidate for a hypoxia-mimicking molecule in LOP strategy.


2017 ◽  
Vol 2017 ◽  
pp. 1-17 ◽  
Author(s):  
Nagarajan Selvamurugan ◽  
Zhiming He ◽  
Daniel Rifkin ◽  
Branka Dabovic ◽  
Nicola C. Partridge

Pulsed electromagnetic fields (PEMFs) have been documented to promote bone fracture healing in nonunions and increase lumbar spinal fusion rates. However, the molecular mechanisms by which PEMF stimulates differentiation of human bone marrow stromal cells (hBMSCs) into osteoblasts are not well understood. In this study the PEMF effects on hBMSCs were studied by microarray analysis. PEMF stimulation of hBMSCs’ cell numbers mainly affected genes of cell cycle regulation, cell structure, and growth receptors or kinase pathways. In the differentiation and mineralization stages, PEMF regulated preosteoblast gene expression and notably, the transforming growth factor-beta (TGF-β) signaling pathway and microRNA 21 (miR21) were most highly regulated. PEMF stimulated activation of Smad2 and miR21-5p expression in differentiated osteoblasts, and TGF-β signaling was essential for PEMF stimulation of alkaline phosphatase mRNA expression. Smad7, an antagonist of the TGF-β signaling pathway, was found to be miR21-5p’s putative target gene and PEMF caused a decrease in Smad7 expression. Expression of Runx2 was increased by PEMF treatment and the miR21-5p inhibitor prevented the PEMF stimulation of Runx2 expression in differentiating cells. Thus, PEMF could mediate its effects on bone metabolism by activation of the TGF-β signaling pathway and stimulation of expression of miR21-5p in hBMSCs.


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