摘要:
The present invention relates to methods, agents and compound screening assays for inducing differentiation of undifferentiated mammalian cells into osteoblasts. The invention thus provides a method, comprising contacting a compound with a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID No: 194-309; and measuring a compound-polypeptide property related to the differentiation of said cells. The invention further relates to a bone formation enhancing pharmaceutical composition, and the use thereof in treating and/or preventing a disease involving a systemic or local decrease in mean bone density in a subject. Furthermore, the invention relates to a method for the in vitro production of bone tissue.
摘要翻译:本发明涉及用于诱导未分化的哺乳动物细胞分化成成骨细胞的方法,试剂和化合物筛选试验。 因此,本发明提供了一种方法,包括使化合物与包含选自SEQ ID No:194-309的氨基酸序列的多肽接触; 并测量与所述细胞的分化相关的化合物 - 多肽性质。 本发明进一步涉及增强骨形成的药物组合物,以及其在治疗和/或预防受试者的全身或局部平均骨密度降低的疾病中的用途。 此外,本发明涉及体外生产骨组织的方法。
摘要:
The present invention relates to in vivo and in vitro methods, agents and compound screening assays for inducing differentiation of undifferentiated mammalian cells into osteoblasts, including bone formation enhancing pharmaceutical compositions, and the use thereof in treating and/or preventing a disease involving a systemic or local decrease in mean bone density in a subject.
摘要:
The present invention relates to in vivo and in vitro methods, agents and compound screening assays for inducing differentiation of undifferentiated mammalian cells into osteoblasts, including bone formation enhancing pharmaceutical compositions, and the use thereof in treating and/or preventing a disease involving a systemic or local decrease in mean bone density in a subject.
摘要:
A compound having a polysaccharide binding domain such as contained by a cellulose and essentially lacking in polysaccharidase activity is purified from other ingredients in a mixture using an affinity partition system. A mixture containing the compound is contacted with a system containing as a first phase an aqueous solution of oligosaccharide polymer such as cellulose and as a second phase a solution of a polymer such as a poly(ethylene glycol)-poly(propylene glycol) copolymer. The compound petitions into the first phase and binds to the oligosaccharide polymer, preferably with a Ka of 103 to 107, to form a complex. The complex is collected, and the compound is dissociated from the oligosaccharide polymer. The compound may be formed of a non-peptide chemical moiety or a peptide moiety linked to a polypeptide having the polysaccharide binding domain. The compound may also be a fusion polypeptide containing the polysaccharide binding domain linked through a protease recognition sequence to a macromolecule such as an enzyme, a hormone or an antibody. The macromolecule can be removed by using a protease to cleave the recognition sequence. Another partition system contains the oligosaccharide polymer and a phase separation inducing agent such as a sulfate or citrate salt that induces separation to produce different phases.
摘要:
The present invention relates to in vivo and in vitro methods, agents and compound screening assays for inhibiting extra-cellular matrix degradation, including joint degenerative inhibiting and/or anti-inflammatory pharmaceutical compositions, and the use thereof in treating and/or preventing a disease involving extra-cellular matrix degradation in a subject.
摘要:
The application discloses methods for identifying and using compounds that inhibit extra-cellular matrix (ECM) degradation and inflammation, using a polypeptide sequence including SEQ ID NO: 17-127 (hereinafter “TARGETS”) and fragments thereof, expression inhibitory agents such as antisense polynucleotide, a ribozyme, and a small interfering RNA (siRNA), comprising a nucleic acid sequence complementary to, or engineered from, a naturally occurring polynucleotide sequence encoding a polypeptide of SEQ ID NO: 17-127, useful in pharmaceutical compositions comprising said agent, for the treatment, or prevention, of chronic joint degenerative and/or inflammatory diseases such as rheumatoid arthritis.
摘要:
A two-phase partition system is provided for affinity separation of a composition containing a polysaccharide binding peptide from a mixture such as a fermentation broth. The peptide may be from an enzyme and lacking in polysaccharidase activity such as the binding domain of cellulase that binds to cellulose. The system contains a phase-forming oligosaccharide polymer such as a cellulose derivative to which the peptide binds with a Ka of 10.sup.3 M to 10.sup.7 M, and a phase inducing agent such as a polyethylene glycol polymer, or a salt present at sufficiently high concentration to induce phase separation. If the oligosaccharide polymer is thermoseparating, phase separation can be induced by heating. Using the system involves contacting a composition containing the peptide such as a fusion protein with the system, partitioning the composition into a phase containing the oligosaccharide polymer by binding to the polymer and recovering the polymer containing the bound composition. The peptide or a fusion protein containing the peptide can be contacted with a cell having a carbohydrate residue to which the peptide binds to form a complex, and the complex is separated with the system to produce a bound cell composition. The peptide may be linked through a protease recognition sequence to a macromolecule such as an enzyme, a hormone or an antibody, and the macromolecule can be removed by using a protease to cleave the recognition sequence.
摘要:
The present invention relates to in vivo and in vitro methods, agents and compound screening assays for inducing anabolic stimulation of chondrocytes, including cartilage formation enhancing pharmaceutical compositions, and the use thereof in treating and/or preventing a disease involving a systemic or local decrease in mean cartilage thickness in a subject.
摘要:
The present invention relates to a method for promoting osteogenesis by contacting osteoblast progenitor cells with an LXR agonist. Said method is useful for the treatment or prevention of an imbalance in bone homeostasis in a subject using bone homeostasis-promoting compositions comprising an effective osteogenic stimulating amount of an LXR agonist in admixture with a pharmaceutically acceptable carrier. A further aspect is a method to produce bone tissue in vitro by contacting an LXR agonist with a population of osteoblast progenitor cells on a substrate, for a time sufficient to stimulate the generation of a matrix of bone tissue.
摘要:
Methods are disclosed for identifying osteogenic promoting compounds by contacting test compounds with a target gene polypeptide or fragment thereof, which target gene is identified as involved in the osteogenesis process, and measuring a compound-polypeptide osteogenesis property. Also disclosed are methods of promoting osteogenesis by contacting progenitor cells with an effective osteogenic stimulating amount of an agonist of a target gene or an expressible nucleic acid of SEQ ID NO. 1-18, and may be used for the treatment or prevention of an imbalance in bone homeostasis. A further aspect is a method to produce bone tissue in vitro, by contacting a target gene agonist or an expressible nucleic acid of SEQ ID NO. 1-18 with a vertebrate cell population including osteoblast progenitor cells on a substrate.
摘要翻译:公开了通过使测试化合物与靶基因多肽或其片段接触来鉴定成骨促进化合物的方法,所述靶基因被鉴定为参与成骨过程,并测量化合物 - 多肽成骨性质。 还公开了通过使祖细胞与有效成骨刺激量的靶基因的激动剂或SEQ ID NO.1的可表达核酸接触来促进成骨的方法。 1-18,可用于治疗或预防骨平衡不稳定。 另一方面是通过使靶基因激动剂或可表达的核酸SEQ ID NO:1的接触,在体外产生骨组织的方法。 1-18具有脊椎动物细胞群,包括在底物上的成骨细胞祖细胞。