scholarly journals Bone Morphogenetic Protein-2 Signaling in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Induced by Pulsed Electromagnetic Fields

2020 ◽  
Vol 21 (6) ◽  
pp. 2104 ◽  
Author(s):  
Fernanda Martini ◽  
Agnese Pellati ◽  
Elisa Mazzoni ◽  
Simona Salati ◽  
Gaetano Caruso ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Bmp Signaling ◽  
Bone Morphogenetic Protein 2 ◽  
Pulsed Electromagnetic Fields ◽  
Synergistic Activity ◽  
Molecular Events ◽  
Morphogenetic Protein ◽  
Pulsed Electromagnetic

Pulsed electromagnetic fields (PEMFs) are clinically used with beneficial effects in the treatment of bone fracture healing. This is due to PEMF ability to favor the osteogenic differentiation of mesenchymal stem cells (MSCs). Previous studies suggest that PEMFs enhance the osteogenic activity of bone morphogenetic protein-2 (BMP2) which is used in various therapeutic interventions. This study investigated the molecular events associated to the synergistic activity of PEMFs and BMP2 on osteogenic differentiation. To this aim, human MSCs (hMSCs) were exposed to PEMFs (75 Hz, 1.5 mT) in combination with BMP2, upon detection of the minimal dose able to induce differentiation. Changes in the expression of BMP signaling pathway genes including receptors and ligands, as well as in the phosphorylation of BMP downstream signaling proteins, such as SMAD1/5/8 and MAPK, were analyzed. Results showed the synergistic activity of PEMFs and BMP2 on osteogenic differentiation transcription factors and markers. The PEMF effects were associated to the increase in BMP2, BMP6, and BMP type I receptor gene expression, as well as SMAD1/5/8 and p38 MAPK activation. These results increase knowledge concerning the molecular events involved in PEMF stimulation showing that PEMFs favor hMSCs osteogenic differentiation by the modulation of BMP signaling components.

scholarly journals Aged human mesenchymal stem cells: the duration of bone morphogenetic protein-2 stimulation determines induction or inhibition of osteogenic differentiation

2014 ◽  
Vol 6 (2) ◽  
Author(s):  
Jostein Heggebö ◽  
Florian Haasters ◽  
Hans Polzer ◽  
Christina Schwarz ◽  
Maximilian Michael Saller ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Culture ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Bone Morphogenetic Protein 2 ◽  
Calcium Deposition ◽  
Experimental Conditions ◽  
Morphogenetic Protein ◽  
Culture Supernatants

Bone morphogenetic protein 2 (BMP-2) is a potent osteoinductive cytokine and a growing number of i<em>n vitro</em> studies analyze its effects on human mesenchymal stem cells (hMSC) derived from aged or osteoporotic donors. In these studies the exact quantification of osteogenic differentiation capacity is of fundamental interest. Nevertheless, the experimental conditions for osteogenic differentiation of aged hMSC have not been evaluated systematically and vary to a considerable extend. Aim of the study was to assess the influence of cell density, osteogenic differentiation media (ODM) change intervals and duration of BMP-2 stimulation on osteoinduction. Furthermore, time series were carried out for osteogenic differentiation and BMP-2 concentration in ODM/BMP-2 cell culture supernatants. The experiments were performed using hMSC isolated from femoral heads of aged patients undergoing hip joint replacement. ODM change intervals of 96 hours resulted in significantly higher calcium deposition compared to shorter intervals. A cell density of 80% prior to stimulation led to stronger osteoinduction compared to higher cell densities. In ODM, aged hMSC showed a significant induction of calcium deposition after 9 days. Added to ODM, BMP-2 showed a stable concentration in the cell culture supernatants for at least 96 hours. Addition of BMP-2 to ODM for the initial 4 days led to a significantly higher induction of osteogenic differentiation compared to ODM alone. On the other hand, addition of BMP-2 for 21 days almost abrogated the osteoinductive effect of ODM. We could demonstrate that the factors investigated have a substantial impact on the extent of osteogenic differentiation of aged hMSC. Consequently, it is of upmost importance to standardize the experimental conditions in order to enable comparability between different studies. We here define standard conditions for osteogenic differentiation in regard to the specific features of aged hMSC. The finding that BMP-2 induces or inhibits osteogenic differentiation in a time dependent manner indicates an age related alteration in signal transduction of hMSC and requires further investigation.

scholarly journals Bone Morphogenetic Protein-2 Accelerates Osteogenic Differentiation in Spheroid-Derived Mesenchymal Stem Cells

2018 ◽  
Vol 27 (4) ◽  
pp. 343-350 ◽  
Author(s):  
Naoyuki Miyaguchi ◽  
Hiroshi Kajiya ◽  
Masahiro Yamaguchi ◽  
Ayako Sato ◽  
Madoka Yasunaga ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein
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