41 results about "DKK1" patented technology

The invention discloses a kit for juvenile osteoporosis detection. Through gene comparison, the fact that compared with a DKK1 gene in the normal people group, a juvenile form osteoporosis patient has the obvious mutant site is discovered, and the obvious mutant site is the 721 site. Through detecting the mutant site, particularly through the pair of provided specific primer pair, whether the people has the juvenile form osteoporosis symptom or not can be specifically identified. Compared with the prior art, the detection method has the advantages that the detection is convenient; accuracy and high speed are realized; the kit is suitable for being popularized and used.

To identify molecular determinants of lytic bone disease in multiple myeloma, the expression profiles of ˜12,000 genes in CD138-enriched plasma cells from newly diagnosed multiple myeloma patients exhibiting no radiological evidence of lytic lesions (n=28) were compared to those with ≧3 lytic lesions (n=47). Two secreted WNT signaling antagonists, soluble frizzled related protein 3 (SFRP-3/FRZB) and the human homologue of Dickkopf-1 (DKK1), were expressed in 40 of 47 with lytic bone lesions, but only 16 of 28 lacking bone lesions (P<0.05). DKK1 and FRZB were not expressed in plasma cells from 45 normal bone marrow donors or 10 Waldenstrom's macroglobulinemia, a related plasma cells malignancy that lacks bone disease. These data indicate that these factors are important mediators of multiple myeloma bone disease, and inhibitors of these proteins may be used to block bone disease.

The invention discloses a time-resolved fluoroimmunoassay used for detecting Dkk1 and a kit thereof. The fluoroimmunoassay includes the following steps: 1. solid-phase anti-body preparing; 2) europium ion marker antibody preparing; and 3) the assay method: based on the double anti-body sandwiched immunoreaction. The invention has the advantages of relatively high sensitivity, specificity and stability on detection of Dkk1; the invention also has a supermatic analytical system which can not only enhance the speed of clinical test results, but also significantly reduce the personal errors and improve the reliability of the test results.

To identify molecular determinants of lytic bone disease in multiple myeloma, the expression profiles of ˜12,000 genes in CD138-enriched plasma cells from newly diagnosed multiple myeloma patients exhibiting no radiological evidence of lytic lesions (n=28) were compared to those with ≧3 lytic lesions (n=47). Two secreted WNT signaling antagonists, soluble frizzled related protein 3 (SFRP-3/FRZB) and the human homologue of Dickkopf-1 (DKK1), were expressed in 40 of 47 with lytic bone lesions, but only 16 of 28 lacking bone lesions (P<0.05). DKK1 and FRZB were not expressed in plasma cells from 45 normal bone marrow donors or 10 Waldenstrom's macroglobulinemia, a related plasma cells malignancy that lacks bone disease. These data indicate that these factors are important mediators of multiple myeloma bone disease, and inhibitors of these proteins may be used to block bone disease reduce tumor burden in multiple myeloma and to block bone disease.

The invention provides a method of treating liver cancer comprising administering anti-DKK1 monoclonal antibody to a subject in need thereof. Anti-DKK1 monoclonal antibody can also be administered for preventing or ameliorating cancer metastasis and for neutralizing serum and tissue DKK1 in liver cancer patients. The use of anti-DKK1 monoclonal antibodies is based on the discovery of the upregulation of DKK1 in human liver cancer.

The invention provides methods of inhibiting hair growth in a post-natal subject by contacting a matured hair follicle cell with a DKK polypeptide. The inhibitory mechanism induced by a DKK polypeptide results in a reversible, transient inhibition of hair growth.

To identify molecular determinants of lytic bone disease in multiple myeloma, the expression profiles of ˜12,000 genes in CD138-enriched plasma cells from newly diagnosed multiple myeloma patients exhibiting no radiological evidence of lytic lesions (n=28) were compared to those with ≧3 lytic lesions (n=47). Two secreted WNT signaling antagonists, soluble frizzled related protein 3 (SFRP-3/FRZB) and the human homologue of Dickkopf-1 (DKK1), were expressed in 40 of 47 with lytic bone lesions, but only 16 of 28 lacking bone lesions (P<0.05). DKK1 and FRZB were not expressed in plasma cells from 45 normal bone marrow donors or 10 Waldenstrom's macroglobulinemia, a related plasma cells malignancy that lacks bone disease. These data indicate that these factors are important mediators of multiple myeloma bone disease, and inhibitors of these proteins may be used to block bone disease.

The invention discloses a pair of small guide RNAs (Ribonucleic Acids) (sgRNAs) for specifically identifying a sheep DKK1 gene and coded DNA (Deoxyribonucleic Acid) and application of the sgRNAs. The sgRNA pair consists of sgRNA-F and sgRNA-R, wherein the sgRNA-F and the sgRNA-R consist of 101 nucleotides respectively; 20nt RNA fragments on a 5' terminal can be used for identifying DKK1 genes on sheep chromosomes, and the remaining 81nt RNA fragments are framework RNA fragments which can be combined with Cas9n nuclease; the sgRNA-F is shown as a sequence 2 in a sequence table, and the sgRNA-R is shown as a sequence 4 in the sequence table. A Cas9 system is used for knocking out or modifying the sheep DKK1 gene on a cell or individual level in order to analyze the function of the sheep DKK1 gene and construct a sheep DKK1 gene mutation database for serving for sheep breeding.

The mechanism by which the high bone mass (HBM) mutation (G171V) of the Wnt coreceptor LRP5 regulates the canonical Wnt signaling was investigated. The mutation was previously shown to reduce Dkk protein-1-mediated antagonism, suggesting that the first YWTD repeat domain where G171 is located may be responsible for Dkk protein-mediated antagonism. However, we found that the third YWTD repeat, but not the first repeat domain, is required for DKK1-mediated antagonism. Instead, we found that the G171V mutation disrupted the interaction of LRP5 with Mesd, a chaperon protein for LRP5/6 that is required for the coreceptors' transport to cell surfaces, resulting in less LRP5 molecules on the cell surface. Although the reduction in the level of cell surface LRP5 molecules led to a reduction in Wnt signaling in a paracrine paradigm, the mutation did not appear to affect the activity of coexpressed Wnt in an autocrine paradigm. Together with the observation that osteoblast cells produce autocrine canonical Wnt, Wnt7b, and that osteocytes produce paracrine Dkk1, we believe that the G171V mutation may cause an increase in Wnt activity in osteoblasts by reducing the number of targets for paracrine Dkk1 to antagonize without affecting the activity of autocrine Wnt.

The present invention provides compositions including reagents for detecting human autoantibodies against at least two proteins selected from the group consisting of ANGTPL4, DKK1, EPHA2, LAMC2, SPON2, SSR2, GAL1, GFRA1, LRRC15, CD147, CD320, CDH3, LRP10, SPINT2, SUSD2, and CST2, and their use in detecting breast cancer or disease recurrence.

The invention discloses an application of DDK1 as a diagnostic marker. Through analysis of a large amount of hepatocellular carcinoma samples, the inventor analyzes the expressions of DKK1 and AFP, firstly discovers that serum DKK1 has a high sensitivity and specificity on diagnosis of hepatocellular carcinoma, especially diagnosis of alpha fetal protein negative hepatocellular carcinoma, identification of hepatocellular carcinoma and alpha fetal protein positive chronic liver disease, and/or diagnosis of hepatocellular carcinoma in the early stage or small hepatocellular carcinoma, and more especially the precision of clinical diagnosis can be largely increased by DKK1-AFP combined diagnosis.

The present invention relates to a method of culturing primitive-like macrophages from stem cells, a kit when used in the method thereof and uses of the primitive like macrophage for in-vitro disease models and for screening compounds for therapy. One embodied culture method comprises contacting and incubating embryonic stem cells or induced pluripotent stem cells with a serum-free culture media comprising a GSK3 inhibitor to differentiate stem cells into cells of the mesoderm lineage, followed by incubation with a culture media comprising Dickkopf-related protein 1 (DKK1) to differentiate the mesoderm into cells of hematopoietic lineage, maturing hematopoietic cells and incubating these cells with a culture media comprising M-CSF to drive differentiation into primitive-like macrophages. Another embodiment comprises incubating the stem cells with serum-free culture media comprising FGF2 and BMP4 to induce differentiation into cells of the mesoderm lineage, followed by incubating the cells with a culture media comprising FGF2, BMP4, Activin A and VEGF to differentiate the cells of the mesoderm lineage into cells of the hematopoietic cell lineage, maturing the cells of the hematopoietic cell lineage and lastly, incubating the matured hematopoietic cells with culture media comprising M-CSF to drive the differentiation of hematopoietic cells into primitive-like macrophages.

The invention provides a screening method of a lung cancer specific transcription regulation and control element. The method comprises the following steps: acquiring epigenetic information in an area about 27kb long surrounding a DKK1 gene locus in a non-small cell lung cancer A549 cell by virtue of a UCSC database, predicting and obtaining 12 candidate enhancer transcription regulation and control element fragments, and respectively inserting the 12 enhancer transcription regulation and control element fragments to the upstream of a near-end promoter of DKK1 to successfully establish luciferase recombinant plasmids; and respectively transfecting the luciferase recombinant plasmids to the non-small cell lung cancer A549 cell, a non-small cell lung cancer H460 cell, a small cell lung cancer H446 cell, an esophagus cancer Eca-109 cell, a normal liver cell Chang liver and a human embryonic kidney cell HEK293, detecting the activity of relevant candidate elements by virtue of a dual-luciferase reporter gene detection system, and screening the regulation and control element having relatively high enhancing expression function on the DKK1 promoter. The screening method has the characteristics of simple operation.

The present invention provides compositions including reagents for detecting human autoantibodies against at least two proteins selected from the group consisting of ANGTPL4, DKK1, EPHA2, LAMC2, SPON2, SSR2, GAL1, GFRA1, LRRC15, CD147, CD320, CDH3, LRP10, SPINT2, SUSD2, and CST2, and their use in detecting breast cancer or disease recurrence.

The invention relates to the field of biomedical treatment, in particular to application of SAP as a diagnostic marker for periodontitis. Inventors of the invention accidentally discover that the SAP plays an important role in occurrence and development of the periodontitis. The inventors deeply research the action and molecular mechanism of the SAP on the periodontitis by using SAP-gene-modified mice, flow cytometry and transcriptome sequencing, and then further discover that the SAP expression of local gingivae of a severe periodontitis patient is increased; after a periodontitis model of an SAP-knocked-out mouse is established, by regulating and controlling M1-type polarization of gingival local macrophages, the activity of osteoclasts is enhanced, the expression of inflammatory factors IL-1beta, IL-6 and TNF-alpha is increased, and the development of the periodontitis is obviously aggravated; and a sequencing result shows that after the SAP is knocked out, the expression of inhibiting factors Sost and Dkk1 of a Wnt/beta-catenin signal channel is up-regulated, and the expression is possibly related to interaction between the macrophages and the osteoblasts.