74 research outputs found
Single nucleotide polymorphisms in bone turnover-related genes in Koreans: ethnic differences in linkage disequilibrium and haplotype
<p>Abstract</p> <p>Background</p> <p>Osteoporosis is defined as the loss of bone mineral density that leads to bone fragility with aging. Population-based case-control studies have identified polymorphisms in many candidate genes that have been associated with bone mass maintenance or osteoporotic fracture. To investigate single nucleotide polymorphisms (SNPs) that are associated with osteoporosis, we examined the genetic variation among Koreans by analyzing 81 genes according to their function in bone formation and resorption during bone remodeling.</p> <p>Methods</p> <p>We resequenced all the exons, splice junctions and promoter regions of candidate osteoporosis genes using 24 unrelated Korean individuals. Using the common SNPs from our study and the HapMap database, a statistical analysis of deviation in heterozygosity depicted.</p> <p>Results</p> <p>We identified 942 variants, including 888 SNPs, 43 insertion/deletion polymorphisms, and 11 microsatellite markers. Of the SNPs, 557 (63%) had been previously identified and 331 (37%) were newly discovered in the Korean population. When compared SNPs in the Korean population with those in HapMap database, 1% (or less) of SNPs in the Japanese and Chinese subpopulations and 20% of those in Caucasian and African subpopulations were significantly differentiated from the Hardy-Weinberg expectations. In addition, an analysis of the genetic diversity showed that there were no significant differences among Korean, Han Chinese and Japanese populations, but African and Caucasian populations were significantly differentiated in selected genes. Nevertheless, in the detailed analysis of genetic properties, the LD and Haplotype block patterns among the five sub-populations were substantially different from one another.</p> <p>Conclusion</p> <p>Through the resequencing of 81 osteoporosis candidate genes, 118 unknown SNPs with a minor allele frequency (MAF) > 0.05 were discovered in the Korean population. In addition, using the common SNPs between our study and HapMap, an analysis of genetic diversity and deviation in heterozygosity was performed and the polymorphisms of the above genes among the five populations were substantially differentiated from one another. Further studies of osteoporosis could utilize the polymorphisms identified in our data since they may have important implications for the selection of highly informative SNPs for future association studies.</p
Abnormal cytokine production by bone marrow stromal cells of multiple myeloma patients in response to RPMI8226 myeloma cells
Isolation and characterisation of human gingival margin-derived STRO-1/MACS+ and MACS− cell populations
Recently, gingival margin-derived stem/progenitor cells isolated via
STRO-1/magnetic activated cell sorting (MACS) showed remarkable periodontal
regenerative potential in vivo. As a second-stage investigation, the present
study's aim was to perform in vitro characterisation and comparison of the
stem/progenitor cell characteristics of sorted STRO-1-positive (MACS+) and
STRO-1-negative (MACS−) cell populations from the human free gingival margin.
Cells were isolated from the free gingiva using a minimally invasive technique
and were magnetically sorted using anti-STRO-1 antibodies. Subsequently, the
MACS+ and MACS− cell fractions were characterized by flow cytometry for
expression of CD14, CD34, CD45, CD73, CD90, CD105, CD146/MUC18 and STRO-1.
Colony-forming unit (CFU) and multilineage differentiation potential were
assayed for both cell fractions. Mineralisation marker expression was examined
using real-time polymerase chain reaction (PCR). MACS+ and MACS− cell
fractions showed plastic adherence. MACS+ cells, in contrast to MACS− cells,
showed all of the predefined mesenchymal stem/progenitor cell characteristics
and a significantly higher number of CFUs (P<0.01). More than 95% of MACS+
cells expressed CD105, CD90 and CD73; lacked the haematopoietic markers CD45,
CD34 and CD14, and expressed STRO-1 and CD146/MUC18. MACS− cells showed a
different surface marker expression profile, with almost no expression of CD14
or STRO-1, and more than 95% of these cells expressed CD73, CD90 and
CD146/MUC18, as well as the haematopoietic markers CD34 and CD45 and CD105.
MACS+ cells could be differentiated along osteoblastic, adipocytic and
chondroblastic lineages. In contrast, MACS− cells demonstrated slight
osteogenic potential. Unstimulated MACS+ cells showed significantly higher
expression of collagen I (P<0.05) and collagen III (P<0.01), whereas MACS−
cells demonstrated higher expression of osteonectin (P<0.05; Mann–Whitney).
The present study is the first to compare gingival MACS+ and MACS− cell
populations demonstrating that MACS+ cells, in contrast to MACS− cells,
harbour stem/progenitor cell characteristics. This study also validates the
effectiveness of the STRO-1/MACS+ technique for the isolation of gingival
stem/progenitor cells. Human free gingival margin-derived STRO-1/MACS+ cells
are a unique renewable source of multipotent stem/progenitor cells
Characterization and purification of osteogenic cells from murine bone marrow by two-color cell sorting using anti-Sca-1 monoclonal antibody and wheat germ agglutinin
Characterization and purification of osteogenic cells from murine bone marrow by two-color cell sorting using anti-Sca-1 monoclonal antibody and wheat germ agglutinin
Characterization of a new antigen of mouse bone marrow stromal cells recognizing osteoprogenitors
Functional and phenotypic differences between CD4+ and CD4- T cell receptor-gamma delta clones from peripheral blood
CD4+ TCR-gamma delta+ T cells comprise a very small subset of TCR-gamma delta+ T cells. CD4+ TCR gamma delta+ T cell clones were established to study the phenotypical and functional characteristics of these cells. Thirty-four CD4+ TCR-gamma delta+ T cell clones were established after sorting CD4+ T cells from a pre-expanded TCR-gamma delta+ T cell population. These clones as well as the CD4- TCR-gamma delta+ T cells from the same donor used V gamma 2 and V delta 2. In a second cloning experiment CD4+ TCR-gamma delta+ T cells were cloned directly from freshly isolated TCR-gamma delta+ T cells using a cloning device coupled to a FACS sorter. Forty-three clones were obtained, which all expressed CD4 and TCR-gamma delta. Eleven of these clones used V delta 1 and three of them coexpressed V gamma 2. The other CD4+ TCR-gamma delta+ T cell clones used both V delta 2 and V gamma 2. CD4+ TCR-gamma delta+ T cell clones expressed CD28 irrespective of the V gamma or V delta usage, and were CD11b negative. Three CD4-CD8+ TCR-gamma delta+ clones expressed CD8 alpha but not CD8 beta and were CD11b positive. CD28 expression among CD4-CD8+ and CD4-CD8- was variable but lower than on CD4+ T cell clones. CD4- TCR-gamma delta+ T cell clones using V gamma 2 and V delta 2 specifically lyse the Burkitt lymphoma cell line Daudi and secrete low levels of IFN-gamma and granulocyte-macrophage-CSF upon stimulation with Daudi. In contrast, most CD4+ T cell clones that use V gamma 2 and V delta 2 had a very low lytic activity against Daudi cells and secrete high levels of IFN-gamma and granulocyte-macrophage-CSF after stimulation with Daudi cells. The NK-sensitive cell line K562 was killed efficiently by the CD4- TCR-gamma delta+ T cell clones, but not by CD4+ TCR-gamma delta+ T cell clones, and could not induce cytokine secretion in CD4+ or CD4- T cell clones. CD4+ TCR-gamma delta+ T cell clones, but not the CD4- clones, could provide bystander cognate T cell help for production of IgG, IgM, and IgA in the presence of IL-2 and IgE in the presence of IL-4. Thus, CD4+ TCR-gamma delta+ T cells are similar to CD4+ TCR-alpha beta+ T cells in their abilities to secrete high levels of cytokines and to provide T cell help in antibody production.(ABSTRACT TRUNCATED AT 400 WORDS
Interleukin 10 inhibits transforming growth factor-beta (TGF-beta) synthesis required for osteogenic commitment of mouse bone marrow cells
- …