Gene expression profile induced by ovariectomy in bone marrow of mice: A functional approach to identify new candidate genes associated to osteoporosis risk in women

Bone ◽  
2014 ◽  
Vol 65 ◽  
pp. 33-41 ◽  
Author(s):  
Begoña Pineda ◽  
Eva Serna ◽  
Andrés Laguna-Fernández ◽  
Inmaculada Noguera ◽  
Layla Panach ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Candidate Genes ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Functional Approach ◽  
Osteoporosis Risk

Gene expression profile of ADAMs and ADAMTSs metalloproteinases in normal and malignant plasma cells and in the bone marrow environment

2011 ◽  
Vol 39 (5) ◽  
pp. 546-557.e8 ◽  
Author(s):  
Caroline Bret ◽  
Dirk Hose ◽  
Thierry Reme ◽  
Alboukadel Kassambara ◽  
Anja Seckinger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Plasma Cells

scholarly journals Analysis of the retinal gene expression profile after hypoxic preconditioning identifies candidate genes for neuroprotection

BMC Genomics ◽  
2008 ◽  
Vol 9 (1) ◽  
pp. 73 ◽  
Author(s):  
Markus Thiersch ◽  
Wolfgang Raffelsberger ◽  
Rico Frigg ◽  
Marijana Samardzija ◽  
Andreas Wenzel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Candidate Genes ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Hypoxic Preconditioning

Novel Murine Model To Study Modulation of Genes and Molecular Pathways Induced Following In Vivo Interaction between Multiple Myeloma Cells and Human BM Milieu.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3409-3409
Author(s):  
Paola Neri ◽  
Pierfrancesco Tassone ◽  
Masood Shammas ◽  
Mariateresa Fulciniti ◽  
Yu-Tzu Tai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Growth ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Murine Model ◽  
Cell Signalling

Abstract Interaction between multiple myeloma (MM) cells and the bone marrow (BM) microenvironment plays a critical role in promoting MM cell growth, survival, migration and development of drug resistance. This interaction within the bone marrow milieu is unique and its understanding is important in evaluating effects of novel agents in vitro and in vivo. We here describe a novel murine model that allows us to study the expression changes in vivo in MM cells within the human BM milieu. In this model, the green fluorescent protein (INA-6 GFP+) transduced IL-6-dependent human MM cell line, INA-6, was injected in human bone chip implanted into SCID mice. At different time points the bone chip was retrieved, cells flushed out and GFP+ MM cells were purified by CD138 MACS microbeads. Similar isolation process was used on INA-6 GFP+ cells cultured in vitro and used as control. Total RNA was isolated from these cells and gene expression profile analyzed using the HG-U133 array chip (Affymetrix) and DChip analyzer program. We have identified significant changes in expression of several genes following in vivo interaction between INA-6 and the BM microenvironment. Specifically, we observed up-regulation of genes associated with cytokines (IL-4, IL-8, IGFB 2–5) and chemokines (CCL2, 5, 6, 18, 24, CCR1, 2, 4), implicated in cell-cell signalling. Moreover genes implicated in DNA transcription (V-Fos, V-Jun, V-kit), adhesion (Integrin alpha 2b, 7, cadherin 1 and 11) and cell growth (CDC14, Cyclin G2, ADRA1A) were also up-regulated and genes involved in apoptosis and cell death (p-57, BCL2, TNF1a) were down-regulated. Using the Ingenuity Pathway Analysis the most relevant pathways modulated by the in vivo interaction between MM cells and BMSCs were IL-6, IGF1, TGF-beta and ERK/MAPK-mediated pathways as well as cell-cycle regulation and chemokine signalling. These results are consistent with previously observed in vitro cell signalling studies. Taken together these results highlight the ability of BM microenvironment to modulate the gene expression profile of the MM cells and our ability to in vivo monitor the changes. This model thus provides us with an ability to study in vivo effects of novel agents on expression profile of MM cells in BM milieu, to pre-clinically characterize their activity.

Novel Model To Evaluate Changes in Gene Expression Profile of Myeloma Cells In Vivo Following Interaction with Human BM Microenvironment.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2490-2490
Author(s):  
Paola Neri ◽  
Pierfrancesco Tassone ◽  
Masood A. Shammas ◽  
Daniel R. Carrasco ◽  
Renate Burger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Cell Growth ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Stromal Cells ◽  
Novel Agents ◽  
Bone Chip

Abstract Multiple Myeloma (MM) cells interact with bone marrow (BM) microenvironment leading to induction of adhesion-mediated and cytokine mediated cell signalling which plays a critical role in promoting MM cell growth, survival, migration and development of drug resistance. We have previously evaluated gene expression changes following interaction between MM cells and BM stromal cells in vitro. However, the interaction between MM cells and microenvironment cells within the bone marrow is unique and its understanding is critical in evaluating effects of novel agents. We here describe a unique model that allows us to analyse in vivo expression changes in MM cells within the human BM milieu; and present preliminary results of expression changes following these in vivo interactions. In this model, BM stromal and IL-6-dependent human MM cell line INA-6 tranduced with GFP (green fluorescent protein) was injected in human fetal bone chip transplanted into SCID mice (SCID-hu mice). The MM cells were allowed to interact with the bone marrow for variable length of time, the bone chip was then retrieved, cells flashed out and GFP+ MM cells were separated by flow cytometry. The GFP negative fraction, containing stromal elements was also separated. Similar flow isolation process was used on INA-6GFP+ cells cultured in vitro and used as control. Total RNA was isolated from these cells and gene expression profile analyzed using the HG-U133 array chip (Affimetrix). We report that interaction between INA-6 cells and the BM microenvironment in vivo induced significant changes in expression profile. In particular, we observed up-regulation of genes implicated in regulation of cell proliferation (RGS 1 and 2, FOS, FOSB, S100A4); DNA transcription (AP1, SWI/SNF related member 1); chromosome organization (Histone1, 2 and 3); cellular trafficking and transport (ARFGEF2, Aquarin 3 and ATPase 4B); and signal transduction (Chemokine ligand 2, 3 and 15, Chemokine receptor 1, 2 and 4, Dual specificity phosphatase 1 and 4, Protein tyrosine phosphatase 1, PIP5-kinase 1A and ZAP70). We also observed down-regulation of genes involved in apoptosis (BCL2-interacting killer, APC, E1A binding protein p300, Fas-associated via death domain, Caspase-activated Dnase, Raf1); and cell-cell adhesion molecules (Cadherin 15, Leupakin, Neurekin, CD44, ICAM2 and PECAM-1a). Although some similarities were observed in gene profile changes following in vitro and in vivo interaction with microenvironment cells, differences were also found. We are now evaluating the effects of interaction on expression profile of stromal cells as well as duration of interaction. Taken together these data confirm the ability of BM microenvironment to modulate gene expression profile of the MM cells in vivo to mediate the MM cell growth, survival and migration. This model now provides us with an opportunity to study effects of novel agents on MM cells expression profile in vivo to pre-clinically characterize their activity.

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