111 results about "RANKL" patented technology

The present invention relates to non-naturally occurring variant Tumor Necrosis Factor Super Family member proteins with reduced immunogenicity. More specifically, the present invention relates to variant BAFF, RANKL, TRAIL, CD40L and APRIL proteins with reduced immunogenicity.

The present invention relates to a method for predicting the risk of a subject developing a cardiovascular event comprising detecting at least one biomarker in (a sample of) the cardiovascular system from said subject, wherein said biomarker comprises at least one protein selected from the group consisting of Tumor Necrosis Factor Alpha Precursor; Lysosomal-associated Membrane Protein (1); Interleukin-5 Precursor; Interleukin-6 Precursor; C-C Motif Chemokine (2) Precursor; C-C Motif Chemokine (5) Precursor RANTES; Cathepsin L1 Precursor; Adenylate Kinase (1); Leukotriene B4 Receptor (1); Complement Factor D; Secreted Phosphoprotein (1); Small Inducible Cytokine A17 Precursor; C-X-C Motif Chemokine (10) Precursor; Tumor Necrosis Factor Ligand Superfamily Member (11)(RANKL); C-C Motif Chemokine (18) Precursor; 72 kDa Type IVCollagenase Precursor; Neutrophil Collagenase Precursor; fatty acid binding protein (4); calpain (2), (m/II) large subunit; Macrophage Migration Inhibitory Factor; Cathepsin S Precursor; Interleukin (13) Precursor; and soluble ICAM-1.

Devices and methods for stimulation of the vagus nerve to modulate (e.g., reduce, suppress, etc.) bone erosion. Methods and apparatus for modulating bone erosion may modulate levels of Receptor Activator for Nuclear Factor κB Ligand (RANKL), and/or to modulate (increase, enhance, etc.) osteoprotegerin (OPG) and/or OPG/RANKL ratio. Devices may include electrical stimulation devices that may be implanted, and may be activated to apply current for a proscribed duration, followed by a period without stimulation.

The invention relates to a RANKL-TNF sample region mouse monoclonal antibody and its preparation method and use. The RANKL-TNF sample region mouse monoclonal antibody is extracted from a RANKL-TNF sample region mouse monoclonal antibody hybridoma cell strain and has the preservation number of CGMCC NO.6853. The RANKL-TNF sample region mouse monoclonal antibody and its related reagents can effectively neutralize TNF-alpha in vitro thereby inhibiting cell apoptosis caused by TNF-alpha, and neutralize RANKL in vitro thereby inhibiting osteoclast generation. The RANKL-TNF sample region mouse monoclonal antibody can effectively relieve an acute inflammation degree, improve bone mass of a mouse suffering from osteoporosis, improve a cancellous bone trabecula microstructure, and effectively improve osteoporosis symptoms.

The invention provides an RANKL-TNF (Receptor Activator of Nuclear Factor Kappa-B Ligand-Tumour Necrosis Factor) sample region fusion protein, and in particular relates to a fusion protein of an RANKL-TNF sample region protein and a Th2 cell epiposition segment with broad host range property. An experiment shows that an antibody produced by an RANKL-TNF sample region fusion protein immune mouse has the effect of combining RANKL with TNF-alpha, can be used for treating diseases such as rheumatoid arthritis and the like and can play effects of antagonistic bone destruction and inflammation inhibition. The RANKL-TNF sample region fusion protein disclosed by the invention can be used as a therapeutic vaccine and provides a new therapeutic approach and thinking for the diseases such as rheumatoid arthritis and the like. According to the invention, the RANKL-TNF sample region fusion protein is expressed in vitro, and therefore the method has the advantages of high expression yield, strong controllability and relatively low production cost;, and the product has good immunogenicity and is easy to realize mass production.

The invention relates to RANKL-Fc fusion protein, a preparation method and the application thereof. The RANKL-Fc fusion protein has P1-P2 or P1-L-P2 structural style; wherein, the P1 is the extracellular region fragment of PANKL protein, P2 is the Fc part of human I g C, and L is linker peptide. The fusion protein provided by the invention can be used for preparing medicines used for treating bone resorption diseases.

The invention discloses a germacrane type sesquiterpene lactone compound, and a preparation method and application thereof. The germacrane type sesquiterpene lactone compound has structural formulas shown as formulas (I) to (IV). In the formulas (I) to (IV), R1 is H or OH; R2 is OH, OMeacr, or OEt; R3 is OAng, OH, or OMeacr; R4 is OTig or OAng; and R5 is CH2OH or CHO. The germacrane sesquiterpenelactone compound provided by the invention has an obvious differentiation inhibition effect on RANKL-induced osteoclasts, the IC50 of most of the compounds is 10.0 [mu]M or below, cytotoxicity is notshown under 10 [mu]M, and the germacrane sesquiterpene lactone can be applied to preparation of drugs for treating and/or preventing osteoporosis and has a good application prospect.

The present invention provides an inhibitor of an autoimmune response to a periodontal bacterial enzymatic degradation product of keratin in gingival epithelium in a mammal having a periodontal bacterium in the oral cavity, containing a substance having affinity to the keratin or a degradation product thereof and/or a substance having affinity to an autoantibody to the degradation product, an agent for the prophylaxis and/or treatment of a periodontal disease and/or a complication thereof; a RANKL expression inhibitor containing a substance having affinity to the keratin or a degradation product thereof; and a method of diagnosing a periodontal disease including detecting the keratin or a degradation product thereof and/or an autoantibody thereto.

The invention discloses an application of nitidine chloride in resisting osteoporosis and in preventing and treating bone loss diseases caused by osteoclasts; the inventor, through researches, discovers that the nitidine chloride can inhibit the formation of the osteoclasts and a bone absorption function in a dose-dependent mode for the first time; it discovers that the nitidine chloride, by intervening RANKL-activated NF-kB and NFAT signaling pathways, can develop an effect of inhibiting the osteoclasts; and by establishing an ovariectomized osteoporosis mouse model, it further provides the effect of the nitidine chloride on the osteoclasts. The nitidine chloride can be used as an ideal medicine for preventing and treating the bone loss diseases caused by the osteoclasts in the future.

The present invention relates to fully humanized antibodies, specifically to a fully human anti-RANKL antibody, a nucleic acid molecule encoding the antibody, and a composition containing the antibody. The present invention further relates to uses of the antibody in preparation of drugs for prevention and treatment of bone loss related diseases, especially osteoporosis, arthritis osteolysis damage or tumor bone metastasis and other diseases. According to the present invention, the antibody is specifically bound with human RANKL and blocks the activity of the human RANKL while the potential immunesuppression of the human RANKL on human body is reduced, the antibody has good stability, and the defect of the non-uniformity (heterogeneity) of the IgG2 antibody production on the batch quality identification is avoided.

The invention discloses a bone-marrow-derived osteoclast culturing method, belonging to the technical field of cell culturing, comprising the steps of: subjecting an extracted bone marrow to treatmentby a separation solution to obtain monocytes, washing, adding a complete culture medium and macrophage colony stimulating factor (M-CSF) to the obtained monocytes, inoculating into a 96-pore plate, and adding a culture medium containing RANKL and M-CSF for culturing on a second day, wherein the complete culture medium is prepared by adding fetal bovine serum and double antibodies into an MEM Alpha basic medium. The bone-marrow-derived osteoclast culturing method has the characteristics of shortened culturing time and reduced culturing cost, so that the monocytes (osteoclast precursor cells) which can be differentiated into osteoclasts and obtained by bone marrow separation have higher purity, the cultured osteoclasts have comparative or even better effect, and the osteoclasts have a widerrange at the respect of enzyme activity and quantity, for providing a finer, more rapid and convenient culture method for screening drugs.

The invention discloses a mouse RANKL (Receptor Activator of Nuclear Factor Kappa B Ligand) mutant as well as establishment, expression and application of an expression carrier of the mutant, provides the mouse RANKL mutant, an establishment method of the expression carrier of the mouse RANKL mutant, and a preparation method for transfecting the expression carrier of the mouse RANKL mutant into a cell, and further provides a cell and an expression system for expressing the expression carrier of the mouse RANKL mutant. The problem in the prior art that the mouse RANKL cannot be conveniently and efficiently studied is solved.

The invention discloses an application of a cyclic polypeptide CST-14 in preparation of a drug for treating osteoporosis. The CST-14 can be directly combined with a key receptor RANK in an osteoporosis process to antagonize an osteoclast induction function caused by RANKL and to play a protective role in the osteoporosis. An in vitro cell experiment result shows that the CST-14 can antagonize an osteoclast differentiation process caused by an osteoporosis key molecule RANKL. Meanwhile, an animal model shows that the CST-14 can inhibit the occurrence of the osteoporosis and improve disease conditions, does not have obvious toxic and side effects after long-term use, can be applied to the field of osteoporosis treatment and has broad application value and market prospect.

The invention discloses a new application of aurantiamide alcohol ester as an MMP-9 inhibitor. Under the condition that the aurantiamide alcohol ester has no cytotoxicity to osteoclast precursor cellsRAW 264.7, the capability of differentiation of RAW 264.7 cells induced by RANKL into osteoclasts is remarkably inhibited, and a certain concentration dependence is shown; follow-up research finds that the aurantiamide alcohol ester significantly reduces the expression of MMP-9 in the osteoclast formation process, thereby inhibiting osteoclast differentiation and formation. The invention discloses the application of the aurantiamide alcohol ester in preventing and treating osteolytic diseases, wherein the aurantiamide alcohol ester can be used for preventing and treating osteolytic diseases including bone destruction, osteoporosis and the like together with a medicine prepared from a conventional medicinal carrier. The invention provides a new medicine for preventing and treating osteoporosis, and has a great clinical application value.

The invention discloses application of kavain in preparing drug for treating osteoporosis. Impact of kavain on osteoclast differentiation, osteoclast absorption and osteoblast differentiaon is evaluated through tartrate-resistant acid phosphatase dyeing, immunofluorescence, reverse transcription-polymerase chain reaction and immunoblotting analysis. Results show that kavain inhibits RANKL inducedosteoclast by blocking NFAT and MAPK passages mediated by calcium while NF-kB is unaffected; kavain also inhibits bone resorption o osteoclast and has no obvious impact on differentiation and proliferation of osteoblast. In addition, kavain can inhibit formation of osteoclast to bone loss of ovariectomized mice. Data display that osteoclast of kavain which is a natural compound has specific effect, which shows that kavain has potential value in treating osteoporosis diseases.

The invention discloses an application of an isoindolone compound in preparation of a medicine for preventing and treating osteolytic diseases. The isoindolone compound has a structure as shown in a formula (I) which is described in the specification. The isoindolone compound can remarkably inhibit the differentiation capacity of bone marrow-derived macrophages BMMs induced by RANKL to osteoclastsand the bone resorption capacity of the osteoclasts, and is concentration-dependent; a subsequent mechanism research finds that the isoindolone compound inhibits expression of a transcription factorNFATc1 by inhibiting activation of RANKL-induced MAPK and PI3K/AKT signal transduction pathways, so that expression of osteoclast related genes is reduced, and the capacity of inhibiting osteoclast differentiation and bone resorption is exerted. Besides, the isoindolone compound does not influence differentiation of osteoblasts, application of the isoindolone compound in prevention and treatment of osteolytic diseases is disclosed, and the isoindolone compound can be used for preventing and treating the osteolytic diseases together with a pharmaceutical composition prepared from a conventionalmedicinal carrier.

The present invention relates to a peptide that binds to RANK and contains the amino acid sequence of the outer surface loop of RANKL. The invention also relates to fragments, analogs and derivatives of this peptide. The invention also relates to compositions containing said peptides. The invention also includes methods of inhibiting osteoclast differentiation, methods of inhibiting bone resorption, and methods of competitively inhibiting RANKL activity. The invention also provides methods of treating diseases or conditions characterized at least in part by loss of bone mass.

The invention discloses an osteoclast vesicle triggered by pH regulation in a closed region and application thereof. The osteoclast can secrete a large number of extracellular vesicles by regulating the pH value of a closed region of osteoclast, and the vesicles are rich in RANK and can be used for antagonizing RANKL, so that the effect of inhibiting the osteoclast is achieved. The osteoclast vesicles are triggered and generated through pH regulation of the closed region, and the mechanism is innovative; the osteoclast-derived vesicles are adopted for osteoclast regulation, so that the method has autologous advantages and high biological safety; the effect is clear, and osteoclast can be effectively inhibited.

The invention discloses application of spermine in preparing a drug for treating periprosthetic osteolysis. Periprosthetic osteolysis occurs after artificial joint replacement. Meanwhile, the invention discloses a pharmaceutical preparation for treating periprosthetic osteolysis. For the application and the pharmaceutical preparation disclosed by the invention, animal experiments prove that the spermine can reduce expression of RANKL, p65, TNF-alpha and IL-1 beta, relieves osteolysis and bone loss induced by titanium particles, confirmed that the spermine has the significant inhibition effecton the osteolysis induced by abrasion particles and can be used as a new means of drug intervention of periprosthetic osteolysis after artificial prosthesis replacement, and thus a new way for treatment of periprosthetic osteolysis is provided.

The invention belongs to the field of health foods, and discloses fishbone collagen peptide calcium noodles and a preparation method thereof. The noodles are prepared from, by weight, 70-80 parts of flour, 10-20 parts of millet flour, 5-10 parts of skim milk powder, 5-10 parts of peanut powder, 0.5-1 part of fructus psoraleae extracts, 0.5-1 part of osteopractic total flavone, 0.1-0.5 part of fishbone collagen peptide calcium chelate, 0.5-1 part of icariin, 0.001-0.005 part of vitamin D and 1-2 parts of table salt. The fishbone collagen peptide calcium noodles prepared by using the method canimprove the bone mineral density of a patient suffering from osteoporosis, and effectively slow the osteoporosis process; moreover, an OPG/RANK/RANKL cell factor system can be regulated through the mediated ROS level so as to inhibit the development of the osteoporosis, and the aim of reducing the occurrence of the osteoporosis is achieved. Therefore, the fishbone collagen peptide calcium noodlesprepared by using the method have the effect of preventing and treating the osteoporosis.