Pharmaceutical compositions and methods of using secreted frizzled related protein
OwnerPeter Bodineinventor
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OwnerPeter Bodineinventor
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Pharmaceutical compositions and methods of use in regulation of mammalian bone forming activities of sFRPs (secreted frizzled-related proteins) are disclosed. sFRPs are secreted receptors for Wnts, which are important polypeptide growth factors that are known to regulate fundamental biological processes like tissue polarity, embryonic development, and tumorigenesis. A sFRP was isolated from human osteoblast cells and identified as sFRP-1 (also known as SARP-2) and shown to be regulated by osteogenic agents in hOB cells in a differentiation selective manner, modulating the life of osteoblasts/preosteocytes. An sFRP-1 knock-out mouse was generated and deletion of sFRP-1 was found to not affect nonskeletal tissues, skeletal morphology or cortical bone development, while resulting in increased trabecular bone formation, decreased osteoblast and osteocyte apoptosis and increased osteoprogenitor differentiation.
A pharmaceutical composition for regulating bone-forming activity in a mammal comprising at least one of (i) a secreted frizzled related protein (sFRP) or regulating portion thereof (ii) an antibody against such proteins or portions thereof, (iii) a nucleic acid that encodes for either (i) or (ii);
A method for identifying a test compound that regulates sFRP activity, which method comprises determining activity of sFRP incubated in a medium containing a test compound, wherein an increase in activity relative to sFRP alone indicates the compound is an sFRP activator and a decrease in activity indicates the compound is an sFRP inhibitor.
A method of facilitating bone formation or repair in a bone cell, comprising introducing a recombinant construct expressing an antisense, siRNA, shRNA sequence to a nucleotide sequence that encodes an sFRP-1 into bone cells.
A method of diagnosing a bone disease or disorder, the method comprising using a polynucleotide probe capable of hybridizing with the polynucleotide having the nucleic acid sequence set forth in SEQ ID NO:
A pharmaceutical composition for regulating bone-forming activity in a mammal comprising at least one antibody to a secreted frizzled related protein (sFRP) or regulating portion thereof.
A method for identifying a test compound that modulates sFRP activity, which method comprises comparing the phenotypic changes induced by the test compound on a sFRP +/+ animal with the phenotypic changes induced by the test compound on a sFRP −/− animal, wherein a phenotypic change in the sFRP +/+animal relative to the sFRP −/− animal indicates the compound is a modulator of sFRP activity.
An immortalized human osteoblast (hOB) cell that expresses a temperature-sensitive mutant of simian virus 40 large T protein antigen, wherein the cell proliferates at about 34° C. but does not proliferate at temperatures exceeding about 37° C., when the T-antigen mutant is inactive.
Dependencies are inferred from the claim text.