Identification of a small molecule kinase inhibitor that enhances osteoblast differentiation of human skeletal (mesenchymal) stem cells through regulation of TGF[beta] signaling

2013 ◽  
Author(s):  
Majken Storm Siersbaek ◽  
Abbas Jafari ◽  
Walid Zaher ◽  
Li Chen ◽  
Moustapha Kassem
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Small Molecule ◽  
Osteoblast Differentiation ◽  
Kinase Inhibitor ◽  
Tgf Beta ◽  
Small Molecule Kinase Inhibitor

scholarly journals A Small-molecule Kinase Inhibitor, CEP-1347, Inhibits Survivin Expression and Sensitizes Ovarian Cancer Stem Cells to Paclitaxel

2018 ◽  
Vol 38 (8) ◽  
pp. 4535-4542 ◽  
Author(s):  
KEITA TOGASHI ◽  
MASASHI OKADA ◽  
MASAHIRO YAMAMOTO ◽  
SHUHEI SUZUKI ◽  
TOMOMI SANOMACHI ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Small Molecule ◽  
Kinase Inhibitor ◽  
Survivin Expression ◽  
Ovarian Cancer Stem Cells ◽  
Small Molecule Kinase Inhibitor

scholarly journals Retinoic and ascorbic acids induce osteoblast differentiation from human dental pulp mesenchymal stem cells

2021 ◽  
Vol 11 (2) ◽  
pp. 143-148
Author(s):  
Lina M. Escobar ◽  
José Daniel Escobar ◽  
Zita Bendahan ◽  
Jaime E. Castellanos
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dental Pulp ◽  
Osteoblast Differentiation ◽  
Human Dental Pulp ◽  
Ascorbic Acids

scholarly journals Condrogenesis of mesenchymal stem cells derived from human amniotic fluid in chitosan-xanthan scaffolds under TGF- beta 3 stimuli

2019 ◽  
Vol 27 ◽  
pp. S433-S434
Author(s):  
I.I. Damas ◽  
C.C. Zuliani ◽  
Â.M. Moraes ◽  
C.B. Westin ◽  
K.C. Andrade ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Amniotic Fluid ◽  
Tgf Beta ◽  
Human Amniotic Fluid

scholarly journals Aging impairs osteoblast differentiation of mesenchymal stem cells grown on titanium by favoring adipogenesis

2016 ◽  
Vol 24 (4) ◽  
pp. 376-382 ◽  
Author(s):  
Rodrigo Paolo Flores ABUNA ◽  
Camila Tami STRINGHETTA-GARCIA ◽  
Leonardo Pimentel FIORI ◽  
Rita Cassia Menegati DORNELLES ◽  
Adalberto Luiz ROSA ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteoblast Differentiation

scholarly journals miR-16-2* Interferes with WNT5A to Regulate Osteogenesis of Mesenchymal Stem Cells

2018 ◽  
Vol 51 (3) ◽  
pp. 1087-1102 ◽  
Author(s):  
Lijun Duan ◽  
He Zhao ◽  
Yang Xiong ◽  
Xiangsheng Tang ◽  
Yongdong Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Osteoblast Differentiation ◽  
Target Genes ◽  
Fragility Fractures ◽  
Inhibitory Effect ◽  
Lymphocytic Leukemia ◽  
Qrt Pcr ◽  
Wnt Signal

Background/Aims: Osteoporosis is a bone metabolic disease characterized by a systemic impairment of bone mass, which results in increased propensity of fragility fractures. A reduction in the differentiation of MSCs into osteoblasts contributes to the impaired bone formation observed in osteoporosis. Mesenchymal stem cells (MSCs) are induced to differentiate into preosteoblasts, which are regulated by the signaling cascades initiated by the various signals, including miRNAs. miR-16-2* is a newly discovered miRNA that participates in diagnosis and prognosis of hepatocellular carcinoma, cervical cancer and chronic lymphocytic leukemia. However, the effect of miR-16-2* on the regulation of osteoblast differentiation and the mechanism responsible are still unclear. Here we discuss the contribution of miR-16-2* to osteoporosis, osteoblast differentiation and mineralization. Methods: The expression pattern of miR-16-2* during osteogenesis or in osteoporosis bone samples was validated by quantitative real-time PCR (qRT-PCR). The human bone marrow mesenchymal stem cells (hBMSCs) were induced to differentiate into osteoblasts by osteogenic induced medium containing dexamethasone, ascorbate-2-phosphat, beta-glycerophosphate and vitamin-D3. The target genes of miR-16-2* were predicted by TargetScan and PicTar. The mRNA and protein levels of osteogenic key markers were detected using qRT-PCR or western blot respectively. The WNT signal activity was analyzed by TOP/FOP reporter assay. Results: The expression of miR-16-2* in patient bone tissue with osteoporosis was negatively correlated with bone formation related genes. During osteoblast differentiation process, the expression of miR-16-2* was significantly decreased. Upregulation of miR-16-2* in hBMSCs impaired the osteogenic differentiation while the downregulation of miR-16-2* increased this process. Upregulation the expression of miR-16-2* could also block the WNT signal pathway by directly target WNT5A. Furthermore, knockdown of miR-16-2* could promote the activation of RUNX2, possibly by lifting the inhibitory effect of miR-16-2* on WNT pathway. Conclusion: Taken together, we report a novel biological role of miR-16-2* in osteogenesis through regulating WNT5A response for the first time. Our data support the potential utilization of miRNA-based therapies in regenerative medicine.

Inhibition of osteoblast differentiation but not adipocyte differentiation of mesenchymal stem cells by sera obtained from aged females

Bone ◽  
2006 ◽  
Vol 39 (1) ◽  
pp. 181-188 ◽  
Author(s):  
Basem M. Abdallah ◽  
Mandana Haack-Sørensen ◽  
Trine Fink ◽  
Moustapha Kassem
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteoblast Differentiation ◽  
Adipocyte Differentiation

scholarly journals Effect of Risedronate on Osteoblast Differentiation, Expression of Receptor Activator of NF-κB Ligand and Apoptosis in Mesenchymal Stem Cells

2011 ◽  
Vol 109 (2) ◽  
pp. 78-84 ◽  
Author(s):  
Hirofumi Fujita ◽  
Kazuko Kurokawa ◽  
Tetsuya Ogino ◽  
Mio Ono ◽  
Masanao Yamamoto ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteoblast Differentiation ◽  
Receptor Activator

scholarly journals Synergistic stimulation of osteoblast differentiation of rat mesenchymal stem cells by leptin and 25(OH)D3 is mediated by inhibition of chaperone-mediated autophagy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qiting He ◽  
Ruixi Qin ◽  
Julie Glowacki ◽  
Shuanhu Zhou ◽  
Jie Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Vitamin D ◽  
Mesenchymal Stem Cells ◽  
Osteoblast Differentiation ◽  
Signal Pathway ◽  
Calcium Deposition ◽  
Qrt Pcr ◽  
Alp Activity ◽  
Chaperone Mediated Autophagy

Abstract Background Vitamin D is important for the mineralization of bones by stimulating osteoblast differentiation of bone marrow mesenchymal stem cells (BMMSCs). BMMSCs are a target of vitamin D action, and the metabolism of 25(OH)D3 to biologically active 1α,25(OH)2D3 in BMMSCs promotes osteoblastogenesis in an autocrine/paracrine manner. Our previous study with human BMMSCs showed that megalin is required for the 25(OH)D3-DBP complex to enter cells and for 25(OH)D3 to stimulate osteoblast differentiation in BMMSCs. Furthermore, we reported that leptin up-regulates megalin in those cells. Leptin is a known inhibitor of PI3K/AKT-dependent chaperone-mediated autophagy (CMA). In this study, we tested the hypothesis that leptin acts synergistically with 25(OH)D3 to promote osteoblastogenesis in rat BMMSCs by a mechanism that entails inhibition of PI3K/AKT-dependent CMA. Methods BMMSCs were isolated from rat bone marrow (4-week-old male SD rats); qRT-PCR and western immunoblots or immunofluorescence were used to evaluate the expression of megalin, ALP, COL1A1, RUNX2, OSX, OSP, and CMA in rBMMSCs. The osteoblast differentiation was evaluated by ALP activity, ALP staining, and calcium deposition. The viability of rBMMSCs was assessed with the CCK-8 kit. Biosynthesis of 1α,25(OH)2D3 was measured by a Rat 1α,25(OH)2D3 ELISA Kit. Results The combination of leptin and 25(OH)D3 treatment significantly enhanced osteoblast differentiation as shown by ALP activity, ALP staining, and calcium deposition, the expression of osteogenic genes ALP, COL1A1, RUNX2, OSX, and OSP by qRT-PCR and western immunoblots in rBMMSCs. Leptin enhanced the expression of megalin and synthesis of 1α,25(OH)2D3 in rBMMSCs. Our data showed that leptin inhibited CMA activity of rBMMSCs by activating PI3K/AKT signal pathway; the ability of leptin to enhance 25(OH)D3 promoted osteoblast differentiation of rBMMSCs was weakened by the PI3K/AKT signal pathway inhibitor. Conclusions Our data reveal the mechanism by which leptin and 25(OH)D3 promote osteoblast differentiation in rBMMSCs. Leptin promoted the expression of megalin by inhibiting CMA, increased the utilization of 25(OH)D3 by rBMMSCs, and enhanced the ability of 25(OH)D3 to induce osteoblast differentiation of rBMMSCs. PI3K/AKT is at least partially involved in the regulation of CMA. These data indicate the importance of megalin in BMMSCs for vitamin D’s role in skeletal health.

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