scholarly journals Extracorporeal shock wave promotes activation of anterior cruciate ligament remnant cells and their paracrine regulation of bone marrow stromal cells’ proliferation, migration, collagen synthesis, and differentiation

2020 ◽  
Vol 9 (8) ◽  
pp. 457-467
Author(s):  
Cheng-Chang Lu ◽  
Shih-Hsiang Chou ◽  
Po-Chih Shen ◽  
Pei-Hsi Chou ◽  
Mei-Ling Ho ◽  
...  
Keyword(s):  
Cell Viability ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Cruciate Ligament ◽  
Marrow Stromal Cells ◽  
Collagen Gene ◽  
Paracrine Regulation ◽  
Tenogenic Differentiation ◽  
Extracorporeal Shock Wave ◽  
Anterior Cruciate

Aims Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells. Methods Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm2, 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)’ viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene ( Scx, TNC) expression were investigated using coculture system. Results ESW-treated ACL remnant cells presented higher cell viability, proliferation, migration, and increased expression of COL-I A1, TGF-β, and VEGF. BMSC proliferation and migration rate significantly increased after coculture with ACL remnant cells with and without ESW stimulation compared to the BMSCs alone group. Furthermore, ESW significantly enhanced ACL remnant cells’ capability to upregulate the collagen gene expression and tenogenic differentiation of BMSCs, without affecting cell viability, TGF-β, and VEGF expression. Conclusion ACL remnant cells modulated activity and differentiation of surrounding cells. The results indicated that ESW enhanced ACL remnant cells viability, proliferation, migration, and expression of collagen, TGF-β, VEGF, and paracrine regulation of BMSC proliferation, migration, collagen expression, and tenogenesis. Cite this article: Bone Joint Res 2020;9(8):457–467.

scholarly journals Identification of Pathways Mediating Growth Differentiation Factor5-Induced Tenogenic Differentiation in Human Bone Marrow Stromal Cells

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0140869 ◽  
Author(s):  
Sik-Loo Tan ◽  
Tunku Sara Ahmad ◽  
Wuey-Min Ng ◽  
Amir Abbas Azlina ◽  
Mahmood Merican Azhar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Tenogenic Differentiation

Green Tea Extract EGCG Induces Apoptosis in CLL Cells and Overcomes the Supportive Effect of Primary Bone Marrow Stromal Cells Through the Regulation of PI3K/Akt Cascade and Proteasome Activity

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3916-3916 ◽  
Author(s):  
Elena Ponath ◽  
Susanne Schnabl ◽  
Martin Hilgarth ◽  
Dita Demirtas ◽  
Marlies Reiter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Viability ◽  
Green Tea ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Cell Killing ◽  
Marrow Stromal Cells ◽  
Proteasome Activity ◽  
Leukemic Cells ◽  
Tea Extract

Abstract Abstract 3916 There is accumulating evidence that green tea extract EGCG [(-)-epigallocatechin-3-gallate] may exert a preventive or a direct anti-tumor effect in several tumor types including chronic lymphocytic leukemia (CLL) and clinical trials with EGCG are already on-going. However, EGCG has a broad spectrum of activities and downstream targets. Therefore, it would be necessary to precisely characterize the key targets of this compound and identify the CLL patients who would most likely profit from EGCG. Therefore, the aim of this study was to evaluate the effect of EGCG on the viability of CLL cells in a well characterized cohort of patients and to get insight into its mechanism of action in CLL. Peripheral blood mononuclear cells (PBMC) of 27 CLL patients were included in this study. Patients were characterized according to the Rai/Binet stage, IgVH mutation status and cytogenetics (13q-del, 11q-del, 17p-del, trisomy-12). The percentage of the leukemic cells (CD19+/CD5+) ranged between 60–98%. CLL cells were exposed to a wide range of concentrations of EGCG (0.1 – 200μM) and cell viability was evaluated by cell titer blue (CTB) assays and FACS analysis after 4 hours, 1, 2 and 3 days. Treatment with EGCG was performed in suspension cultures and under co-culture with primary human bone marrow stromal cells (BMSC). Cell viability assays demonstrated a dose and time dependent decrease in the cell viability after the exposure to EGCG with an IC50 ranging between 50–80μM (25–50μg/ml). A moderate variation in the response to EGCG was observed between patients demonstrating the heterogeneity of the disease. No clear correlation between the in vitro response to EGCG and the clinical background and prognostic markers could be observed in this cohort of patients. Annexin V/propidium iodide (Anx/PI) staining showed that EGCG increased the percentage of early apoptotic (Anx+/PI-) and late apoptotic/necrotic cells (Anx+/PI+). These data suggest that EGCG exerts a pro-apoptotic effect and activates other cell killing mechanisms in CLL cells. The leukemic cells (CD19/CD5) were relatively more sensitive to the compound compared to T cells and monocytes. Co-culture experiments showed that EGCG effectively overcomes the supportive effect of BMSC and induces apoptosis/cell killing in CLL cells. BMSC were less sensitive to the compound and a toxic effect was observed at a concentration of 200 μM or higher. RT-PCR showed a downregulation of the catalytic domain p110a and the regulatory domain p85 of phosphoinositide 3-kinases (PI3K) as well as Bcl-2 and Mcl-1 mRNA expression after exposure to EGCG. Western blotting analysis demonstrated a decrease in the phosphorylation of Akt particularly at pThr308 residue and de-phosphorylation of the tumor suppressor PTEN at pSer380 residue in parallel to the induction of PARP cleavage. In addition, EGCG induced a decrease in the protein expression of the activation marker CD23 and the adhesion molecule CD44. Furthermore, proteasome assays showed that EGCG inhibits the chymotrypsin-like activity within 4 hours of incubation in parallel to induction of early apoptosis. This effect was more remarkable after 24 hours. However, EGCG was less effective in proteasome inhibition compared to Bortezomib. In conclusion, these data demonstrate that EGCG induces cell death in CLL cells through a complex mechanism which may involve the inactivation of PI3K/Akt signaling cascade and inhibition of proteasome activity. The results also point to a potential therapeutic effect of EGCG in CLL which warrants further evaluation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Fate of tenogenic differentiation potential of human bone marrow stromal cells by uniaxial stretching affected by stretch-activated calcium channel agonist gadolinium

PLoS ONE ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. e0178117 ◽  
Author(s):  
Hui Yin Nam ◽  
Hanumantha Rao Balaji Raghavendran ◽  
Belinda Pingguan-Murphy ◽  
Azlina A. Abbas ◽  
Azhar M. Merican ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Calcium Channel ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Differentiation Potential ◽  
Uniaxial Stretching ◽  
Tenogenic Differentiation

scholarly journals Advanced glycosylation end products inhibit the proliferation of bone-marrow stromal cells through activating MAPK pathway

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Zheng Li ◽  
Xiao Wang ◽  
Tian-pei Hong ◽  
Hao-jie Wang ◽  
Zhan-yi Gao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Protein Kinase ◽  
Cell Viability ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Mapk Pathway ◽  
Marrow Stromal Cells ◽  
Advanced Glycosylation End Products ◽  
End Products ◽  
Advanced Glycosylation

Abstract Background The purpose of present study was to explore the mechanism of nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B(PKB/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways after intervention of advanced glycosylation end products (AGEs) on rat bone-marrow stromal cells (BMSCs). Methods Prepare and identify AGEs. BMSCs were isolated from 16 SD rats and cultured with different concentration of AGEs. Cell viability was detected by cell counting kit-8 (CCK-8). BMSCs were cultured with AGEs (0.25 mg/ml) for 30 min, 12 h, 24 h, 72 h and 120 h. In addition, BMSCs were cultured with AGEs, AGEs + JNK inhibitor and AGEs + P38 inhibitor for 24 h and 48 h, respectively. Western blotting and RT-PCR were used to determine the protein and mRNA expression levels, respectively. Results Cell viability of BMSCs was significantly correlated with concentration and effect time of AGEs (P < 0.05), and the most appropriate concentration was 0.25 mg/ml. AGEs stimulation significantly increased the protein expression levels of NF-κB p65, JNK, p38 (P < 0.05), decreased IκB (P < 0.05), but had no effect on the protein expression of Akt in BMSCs (P > 0.05). At the mRNA level, JNK and p38 inhibitors significantly reduced the levels of NF-κB p65, p38 and JNK, increased IκB (P > 0.05), but had no effect on Akt in BMSCs (P > 0.05). At the protein level, JNK and p38 inhibitors notably decreased the expression of NF-κB p65, p38, p-JNK, P-IκB and JNK (P < 0.001), and increased IκB (P < 0.05). Conclusion Advanced glycosylation end products can inhibit the proliferation of bone-marrow stromal cells through activating MAPK pathway.

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