Journal Articles on Category: Biology and Life Sciences

MicroRNAs (miRNAs) are non-coding RNAs that bind to target mRNA leading to translational arrest or mRNA degradation. To study miRNA-mediated regulation of osteogenesis and chondrogenesis, we compared the expression of 35 miRNAs in osteoblasts and chondroblasts derived from mouse marrow stromal cells (MSCs). Differentiation of MSCs resulted in up- or downregulation of several miRNAs, with miR-199a expression being over 10-fold higher in chondroblasts than in undifferentiated MSCs. In addition, miR-124a was strongly upregulated during chondrogenesis while the expression of miR-96 was substantially suppressed. A systems biological analysis of the potential miRNA target genes and their interaction networks was combined with promoter analysis. These studies link the differentially expressed miRNAs to collagen synthesis and hypoxia, key pathways related to bone and cartilage physiology. The global regulatory networks described here suggest for the ?rst time how miRNAs and transcription factors are capable of ? ne-tuning the osteogenic and chondrogenic differentiation of mouse MSCs.

Issn:11776250

Keywords: MicroRNA ; Marrow stromal cells ; Chondrogenesis ; Osteogenesis

Volume: 2

Pages: 177-191

Abstract Background Neuronal tissue has limited potential to self-renew or repair after neurological diseases. Cellular therapies using stem cells are promising approaches for the treatment of neurological diseases. However, the clinical use of embryonic stem cells or foetal tissues is limited by ethical considerations and other scientific problems. Thus, bone marrow mesenchymal stomal cells (BM-MSC) could represent an alternative source of stem cells for cell replacement therapies. Indeed, many studies have demonstrated that MSC can give rise to neuronal cells as well as many tissue-specific cell phenotypes. Methods BM-MSC were differentiated in neuron-like cells under specific induction (NPBM + cAMP + IBMX + NGF + Insulin). By day ten, differentiated cells presented an expression profile of real neurons. Functionality of these differentiated cells was evaluated by calcium influx through glutamate receptor AMPA3. Results Using microarray analysis, we compared gene expression profile of these different samples, before and after neurogenic differentiation. Among the 1943 genes differentially expressed, genes down-regulated are involved in osteogenesis, chondrogenesis, adipogenesis, myogenesis and extracellular matrix component (tuftelin, AGC1, FADS3, tropomyosin, fibronectin, ECM2, HAPLN1, vimentin). Interestingly, genes implicated in neurogenesis are increased. Most of them are involved in the synaptic transmission and long term potentialisation as cortactin, CASK, SYNCRIP, SYNTL4 and STX1. Other genes are involved in neurite outgrowth, early neuronal cell development, neuropeptide signaling/synthesis and neuronal receptor (FK506, ARHGAP6, CDKRAP2, PMCH, GFPT2, GRIA3, MCT6, BDNF, PENK, amphiregulin, neurofilament 3, Epha4, synaptotagmin). Using real time RT-PCR, we confirmed the expression of selected neuronal genes: NEGR1, GRIA3 (AMPA3), NEF3, PENK and Epha4. Functionality of these neuron-like cells was demonstrated by Ca2+ influx through glutamate receptor channel (AMPA3) in the presence of two agonist glutamate, AMPA or CNQX antagonist. Conclusion Our results demonstrate that BM-MSC have the potential to differentiate in neuronal cells with specific gene expression and functional properties. BM-MSC are thus promising candidates for cell-based therapy of neurodegenerative diseases

Issn:14712164

Keywords:

Volume: 9

Pages: 166

Abstract Background The Gpnmb gene encodes a transmembrane protein whose function(s) remain largely unknown. Here, we assess if a mutant allele of Gpnmb confers susceptibility to glaucoma by altering immune functions. DBA/2J mice have a mutant Gpnmb gene and they develop a form of glaucoma preceded by a pigment dispersing iris disease and abnormalities of the immunosuppressive ocular microenvironment. Results We find that the Gpnmb genotype of bone-marrow derived cell lineages significantly influences the iris disease and the elevation of intraocular pressure. GPNMB localizes to multiple cell types, including pigment producing cells, bone marrow derived F4/80 positive antigen-presenting cells (APCs) of the iris and dendritic cells. We show that APCs of DBA/2J mice fail to induce antigen induced immune deviation (a form of tolerance) when treated with TGFβ2. This demonstrates that some of the immune abnormalities previously identified in DBA/2J mice result from intrinsic defects in APCs. However, the tested APC defects are not dependent on a mutant Gpnmb gene. Finally, we show that the Gpnmb mediated iris disease does not require elevated IL18 or mature B or T lymphocytes. Conclusion These results establish a role for Gpnmb in bone marrow derived lineages. They suggest that affects of Gpnmb on innate immunity influence susceptibility to glaucoma in DBA/2J mice.

Issn:14712156

Keywords:

Volume: 9

Pages: 30

Abstract Background Mesenchymal stem cells (MSCs) have been recently investigated for their potential use in regenerative medicine. MSCs, in particular, have great potential, as in various reports they have shown pluripotency for differentiating into many different cell types. However, the ability of MSCs to differentiate into tendon cells in vitro has not been fully investigated. Results In this study, we show that equine bone marrow mesenchymal stem cells (BM-MSCs), defined by their expression of markers such as Oct4, Sox-2 and Nanog, have the capability to differentiate in tenocytes. These differentiated cells express tendon-related markers including tenomodulin and decorin. Moreover we show that the same BM-MSCs can differentiate in osteocytes, as confirmed by alkaline phosphatase and von Kossa staining. Conclusion As MSCs represent an attractive tool for tendon tissue repair strategies, our data suggest that bone marrow should be considered the preferred MSC source for therapeutic approaches.

Issn:14712121

Keywords:

Volume: 10

Pages: 29

Abstract Background Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. Results We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Conclusion Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.

Issn:1476511X

Keywords:

Volume: 8

Pages: 9

Issn:03774929

Keywords:

Volume: 52

Pages: 290-291

Abstract Background Cell transplantation is likely to become an important therapeutic tool for the treatment of various traumatic and ischemic injuries to the central nervous system (CNS). However, in many pre-clinical cell therapy studies, reporter gene-assisted imaging of cellular implants in the CNS and potential reporter gene and/or cell-based immunogenicity, still remain challenging research topics. Results In this study, we performed cell implantation experiments in the CNS of immunocompetent mice using autologous (syngeneic) luciferase-expressing bone marrow-derived stromal cells (BMSC-Luc) cultured from ROSA26-L-S-L-Luciferase transgenic mice, and BMSC-Luc genetically modified using a lentivirus encoding the enhanced green fluorescence protein (eGFP) and the puromycin resistance gene (Pac) (BMSC-Luc/eGFP/Pac). Both reporter gene-modified BMSC populations displayed high engraftment capacity in the CNS of immunocompetent mice, despite potential immunogenicity of introduced reporter proteins, as demonstrated by real-time bioluminescence imaging (BLI) and histological analysis at different time-points post-implantation. In contrast, both BMSC-Luc and BMSC-Luc/eGFP/Pac did not survive upon intramuscular cell implantation, as demonstrated by real-time BLI at different time-points post-implantation. In addition, ELISPOT analysis demonstrated the induction of IFN-γ-producing CD8+ T-cells upon intramuscular cell implantation, but not upon intracerebral cell implantation, indicating that BMSC-Luc and BMSC-Luc/eGFP/Pac are immune-tolerated in the CNS. However, in our experimental transplantation model, results also indicated that reporter gene-specific immune-reactive T-cell responses were not the main contributors to the immunological rejection of BMSC-Luc or BMSC-Luc/eGFP/Pac upon intramuscular cell implantation. Conclusion We here demonstrate that reporter gene-modified BMSC derived from ROSA26-L-S-L-Luciferase transgenic mice are immune-tolerated upon implantation in the CNS of syngeneic immunocompetent mice, providing a research model for studying survival and localisation of autologous BMSC implants in the CNS by real-time BLI and/or histological analysis in the absence of immunosuppressive therapy.

Issn:14726750

Keywords:

Volume: 9

Pages: 1

The effects of plant density and tiller removal were determined on yield and agronomic characters of 3 sweet corn cultivars during the growing periods in 1997 and 1998 in Isparta plain in Turkey. Ear yield varied depending on cultivars and the highest ear yield was obtained for cv. Merit in 1997 and 1998 (13.8 and 11.8 t ha-1, respectively). Number of tiller plant 1, ear length, ear diameter and filled ear length decreased in high plant density (9.5 plants/m2). Plant height and ear yield increased as the plant density increased. While tiller removal did not affect statistically significant any characters except the filled ear length in sweet corn varieties in 1997. It reduced plant height and ear yield in the second experimental year.

Issn:10288880

Keywords: Zea mays saccharata sturt ; cultivars ; plant density ; tiller removal ; ear yield

Volume: 5

Pages: 906-908

Abstract Background Interaction between hair cells and acellular gels of the mammalian inner ear, the tectorial and otoconial membranes, is crucial for mechanoreception. Recently, otoancorin was suggested to be a mediator of gel attachment to nonsensory cells, but the molecular components of the interface between gels and sensory cells remain to be identified. Hypothesis We report that the inner ear protein stereocilin is related in sequence to otoancorin and, based on its localisation and predicted GPI-anchoring, may mediate attachment of the tectorial and otoconial membranes to sensory hair bundles. Testing It is expected that antibodies directed against stereocilin would specifically label sites of contact between sensory hair cells and tectorial/otoconial membranes of the inner ear. Implications Our findings support a unified molecular mechanism for mechanotransduction, with stereocilin and otoancorin defining a new protein family responsible for the attachment of acellular gels to both sensory and nonsensory cells of the inner ear.

Issn:14712121

Keywords:

Volume: 3

Pages: 28

Abstract Background 5,11,14 20:3 is similar to 20:4n-6 but lacks the internal Δ8 double bond essential for prostaglandin and eicosanoid synthesis. When previously fed to laboratory animals as a gymnosperm seed oil component it has shown anti-inflammatory properties. Results Herein, topically applied Podocarpus nagi methyl esters (containing 26% 5,11,14 20:3) were incorporated into mouse ear phospholipids, reduced 20:4n-6, and reduced 20:4n-6- and TPA-induced mouse ear edema. Purified 5,11,14 20:3 was taken up by cultured human skin keratinocytes, reduced 20:4n-6, and reduced PGE2 levels dramatically. Purified 5,11,14 20:3 did not affect PPARα, PPARγ, or PPARδ transactivation. Conclusions Topical application of 5,11,14 20:3 to skin surfaces can thus reduce inflammatory processes, most likely by displacing 20:4n-6 from phospholipid pools and reducing downstream inflammatory products derived from 20:4n-6 such as PGE2 and leukotrienes. It could have potential use in treating clinical skin disorders resulting from overproduction of 20:4n-6-derived eicosanoid products.

Issn:1476511X

Keywords: 5,11,14 Eicosatrienoate ; Fatty acid ; Non-methylene interrupted fatty acid ; Peroxisome proliferated activated receptor ; Tumor necrosis factor

Volume: 1

Pages: 5