scholarly journals Exendin-4 Induces Bone Marrow Stromal Cells Migration Through Bone Marrow-Derived Macrophages Polarization via PKA-STAT3 Signaling Pathway

2017 ◽  
Vol 44 (5) ◽  
pp. 1696-1714 ◽  
Author(s):  
Ning Wang ◽  
Jian Gao ◽  
Min Jia ◽  
Xue Ma ◽  
Zhanxiang Lei ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Macrophage Polarization ◽  
Marrow Stromal Cells ◽  
Bone Surface ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Tgf Β1

Background/Aims: The synthesis and degradation processes involved in bone remodeling are critically regulated by osteoblasts and osteoclasts. The GLP-1 receptor agonist Exendin-4 is beneficial for osteoblast differentiation and increases the number of osteoblasts. Methods: We constructed an ovariectomized model to evaluate the impact of Exendin-4 on bone formation in osteoporosis. A macrophage-depleted model was also created to investigate the effect of macrophages on bone formation. Thirty-two female WT C57BL/6 mice (aged 3 months) were randomly assigned to a normal control group and four ovariectomized (OVX) subgroups: OVX + vehicle group, OVX + Exendin-4 (4.2 µg/kg/day) group, OVX + chloride phosphate liposome group and OVX + chloride phosphate liposome + Exendin-4 group. Results: In this study, we found that Exendin-4 not only increased the number of osteoblasts and decreased the number of osteoclasts, but also increased the number of bone marrow stromal cells (BMSCs) at the bone surface. Moreover, we found that OVX mice treated with Exendin-4 increased TGF-β1 levels at the bone surface compared with that in OVX mice. Besides, Exendin-4 promoted the polarization of bone marrow-derived macrophages into M2 subtype and increased TGF-β1 secretion by the M2 subtype. Finally, we found that Exendin-4 induced macrophage polarization via the cAMP-PKA-STAT3 signaling pathway. Conclusion: Exendin-4 promotes bone marrow-derived macrophage polarization to the M2 subtype and induces BMSC migration to the bone surface via PKA-STAT3 signaling.

scholarly journals New Bone Formation in Tuberculous-Infected Vertebral Body Defect after Administration of Bone Marrow Stromal Cells in Rabbit Model

2016 ◽  
Vol 10 (1) ◽  
pp. 1 ◽  
Author(s):  
Ahmad Jabir Rahyussalim ◽  
Tri Kurniawati ◽  
Nurjati Chairani Siregar ◽  
Agus Syahrurachman ◽  
Ismail Hadisubroto Dilogo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Vertebral Body ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Rabbit Model ◽  
Marrow Stromal Cells ◽  
New Bone Formation

Localex vivo gene therapy with bone marrow stromal cells expressing human BMP4 promotes endosteal bone formation in mice

2004 ◽  
Vol 6 (1) ◽  
pp. 4-15 ◽  
Author(s):  
Xiao S. Zhang ◽  
Thomas A. Linkhart ◽  
Shin-Tai Chen ◽  
Hairong Peng ◽  
Jon E. Wergedal ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Bone Marrow ◽  
Bone Formation ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells

scholarly journals Bone formation following transplantation of genetically modified primary bone marrow stromal cells

2003 ◽  
Vol 21 (4) ◽  
pp. 630-637 ◽  
Author(s):  
Osamu Sugiyama ◽  
Hideo Orimo ◽  
Satoru Suzuki ◽  
Kazuo Yamashita ◽  
Hiromoto Ito ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Genetically Modified ◽  
Marrow Stromal Cells ◽  
Primary Bone ◽  
Primary Bone Marrow

Nifuroxazide Inhibits STAT3 Function and Shows Potent Anti-Tumor Activity Against Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3450-3450
Author(s):  
Erik A. Nelson ◽  
Teru Hideshima ◽  
Laurie Gashin ◽  
Sarah R. Walker ◽  
Rebecca A. Lynch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Transcriptional Activity ◽  
Marrow Stromal Cells ◽  
Normal Peripheral Blood ◽  
Myeloma Cells ◽  
Stat3 Signaling ◽  
Nf Kappab

Abstract Activation of the transcription factor STAT3 is essential for the pathogenesis of many cancers, including multiple myeloma. While normal cells can tolerate a reduction in STAT3 function, tumors often require constitutive STAT3 signaling for survival. Thus, identifying drugs that inhibit STAT3 activity may provide new therapeutic agents useful for cancer treatment. We have developed a high throughput cell-based screen to identify drugs that inhibit STAT3-dependent transcriptional activity. To assure the specificity of these drugs for STAT3 function, we performed a counter screen assessing NF-kappaB-dependent transcriptional activity. To bypass the difficulties inherent in the development of novel small molecules for clinical use, we analyzed a library of 1120 drugs that are either FDA approved, or are otherwise known to be safe in humans. From this screen, we identified nifuroxazide, a drug used to treat dehydration associated with diarrheal illness, as a potent inhibitor of STAT3 transcriptional activity. By contrast, nifuroxazide has no effect on NF-kappaB-dependent transcription. Myeloma cells containing constitutive STAT3 activation show decreased STAT3 tyrosine phosphorylation when incubated with 10 uM nifuroxazide. In addition, expression of STAT3 target genes necessary for myeloma survival, including bcl-x, mcl-1, and cyclin D1, is markedly reduced by 10 uM nifuroxazide. To determine whether these effects of nifuroxazide on STAT3 signaling alter cell viability, we utilized U266 myeloma cells, which depend on STAT3 activation for survival. U266 viability is inhibited by nifuroxazide at an EC50 of approximately 3 uM. Notably, RPMI 8226 myeloma cells, which do not contain activated STAT3, are not affected by comparable concentrations of nifuroxazide. In addition, this dose has no effect on normal peripheral blood mononuclear cells. Given that myeloma cells receive survival signals from bone marrow stromal cells, we determined if nifuroxazide affects myeloma survival in stromal cell co-cultures. Nifuroxazide is effective at reducing U266 viability in the presence of bone marrow stromal cells at an EC50 of approximately 3 uM. Thus, screening for compounds that inhibit STAT3 transcriptional activity is useful in identifying potential drugs for myeloma therapy. Through this approach, we have identified a novel STAT3 inhibitory function for nifuroxazide. Nifuroxazide inhibits STAT3 mediated survival of myeloma cells and may be useful, either alone or in combination with other drugs, for the treatment of patients with multiple myeloma.

scholarly journals Association between in vivo bone formation and ex vivo migratory capacity of human bone marrow stromal cells

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Rikke K. Andersen ◽  
Walid Zaher ◽  
Kenneth H. Larsen ◽  
Nicholas Ditzel ◽  
Katharina Drews ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Ex Vivo ◽  
Marrow Stromal Cells ◽  
Human Bone ◽  
Migratory Capacity ◽  
In Vivo Bone Formation

scholarly journals Lamellar Spacing in Cuboid Hydroxyapatite Scaffolds Regulates Bone Formation by Human Bone Marrow Stromal Cells

2011 ◽  
Vol 17 (11-12) ◽  
pp. 1615-1623 ◽  
Author(s):  
Mahesh H. Mankani ◽  
Shahrzad Afghani ◽  
Jaime Franco ◽  
Max Launey ◽  
Sally Marshall ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Lamellar Spacing ◽  
Marrow Stromal Cells ◽  
Human Bone ◽  
Human Bone Marrow
Sign in / Sign up

Export Citation Format

Share Document