Claims
- 1. A pharmaceutical composition comprising a carrier and a compound of the formula I:
- 2. The pharmaceutical composition of claim 1, wherein R1, R2, R3, R4, R5, R6, R7, and R8 groups are each separately carbonyl, hydroxy, hydrogen, or lower hydroxy alkyl.
- 3. The pharmaceutical composition of claim 1, wherein R1 is carbonyl or hydroxy.
- 4. The pharmaceutical composition of claim 1, wherein R8 is fluorine, hydrogen or halo.
- 5. A pharmaceutical composition for decreasing SOST expression in a mammal comprising a therapeutically effective amount of a glucocorticoid.
- 6. The pharmaceutical composition of claim 5, wherein the glucocorticoid can bind to the glucocorticoid receptor.
- 7. The pharmaceutical composition of claim 5, wherein the glucocorticoid is fluocinolone acetonide, triamcinolone or dexamethasone.
- 8. A pharmaceutical composition comprising a carrier and a prostaglandin comprising formula II:
- 9. The pharmaceutical composition of claim 8, wherein R1 and R4 are each separately carbonyl, hydroxy, hydrogen, or lower hydroxy alkyl.
- 10. The pharmaceutical composition of claim 8, wherein the prostaglandin is prostaglandin E2.
- 11. A pharmaceutical composition comprising a carrier and a bile salt of formula III:
- 12. The pharmaceutical composition of claim 11, wherein R1, R2, R3, R4, R5, R6, R7 and R9 are each separately carbonyl, hydroxy, hydrogen, or lower hydroxy alkyl.
- 13. The pharmaceutical composition of claim 11, wherein the bile salt is ursodeoxycholic acid.
- 14. A pharmaceutical composition comprising a carrier and a siRNA comprising SEQ ID NO: 11, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 38, SEQ ID NO: 41 or SEQ ID NO: 44, wherein the siRNA can modulate SOST expression.
- 15. A pharmaceutical composition comprising a carrier and a siRNA that is selectively hybridizable under stringent conditions to an RNA derived from a DNA comprising SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 27, SEQ ID NO: 30, SEQ ID NO: 33, SEQ ID NO: 36, SEQ ID NO: 39, or SEQ ID NO: 42, wherein the siRNA can modulate SOST expression.
- 16. A method for modulating SOST expression in a mammal that comprises administering to the mammal ursodeoxycholic acid, fluocinolone acetonide, triamcinolone, prostaglandin E2 or dexamethasone.
- 17. A method for modulating SOST expression in a mammal that comprises administering to the mammal a compound of formula I:
- 18. A method for modulating SOST expression in a mammal that comprises administering to the mammal a compound of formula II:
- 19. A method for modulating SOST expression in a mammal that comprises administering to the mammal a compound of formula III:
- 20. A method for modulating SOST expression in a mammal that comprises administering to the mammal a glucocorticoid.
- 21. The method of claim 20, wherein the glucocorticoid is cortisol or dexamethasone.
- 22. A method for modulating SOST expression in a mammal that comprises administering to the mammal a siRNA comprising SEQ ID NO: 11, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 38, SEQ ID NO: 41 or SEQ ID NO: 44, wherein the siRNA can modulate SOST expression.
- 23. A method for modulating SOST expression in a mammal that comprises administering to the mammal a siRNA that is selectively hybridizable under stringent conditions to an RNA derived from a DNA comprising SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 27, SEQ ID NO: 30, SEQ ID NO: 33, SEQ ID NO: 36, SEQ ID NO: 39, or SEQ ID NO: 42, wherein the siRNA can modulate SOST expression.
- 24. A method for increasing bone density in a mammal that comprises administering ursodeoxycholic acid, fluocinolone acetonide, triamcinolone, prostaglandin E2 or dexamethasone to the mammal.
- 25. A method for increasing bone density in a mammal that comprises administering to the mammal a compound of formula I:
- 26. A method for increasing bone density in a mammal that comprises administering to the mammal a compound of formula II:
- 27. A method for increasing bone density in a mammal that comprises administering to the mammal a compound of formula III:
- 28. A method for increasing bone density in a mammal that comprises administering to the mammal a glucocorticoid, wherein the glucocorticoid modulates SOST expression.
- 29. The method of claim 28, wherein the glucocorticoid is cortisol or dexamethasone.
- 30. A method for increasing bone density in a mammal that comprises administering to the mammal a siRNA comprising SEQ ID NO: 11, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 38, SEQ ID NO: 41 or SEQ ID NO: 44, wherein the siRNA can modulate SOST expression.
- 31. A method for increasing bone density in a mammal that comprises administering to the mammal a siRNA that is selectively hybridizable under stringent conditions to an RNA derived from a DNA comprising SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 27, SEQ ID NO: 30, SEQ ID NO: 33, SEQ ID NO: 36, SEQ ID NO: 39, or SEQ ID NO: 42, wherein the siRNA can modulate SOST expression.
- 32. A method for decreasing apoptosis of bone cells in a mammal that comprises administering ursodeoxycholic acid, fluocinolone acetonide, triamcinolone, prostaglandin E2 or dexamethasone to the mammal.
- 33. A method for decreasing apoptosis of bone cells in a mammal that comprises administering to the mammal a compound of formula I:
- 34. A method for decreasing apoptosis of bone cells in a mammal that comprises administering to the mammal a compound of formula II:
- 35. A method for decreasing apoptosis of bone cells in a mammal that comprises administering to the mammal a compound of formula III:
- 36. A method for decreasing apoptosis of bone cells in a mammal that comprises administering to the mammal a glucocorticoid, wherein the glucocorticoid modulates SOST expression.
- 37. The method of claim 36, wherein the glucocorticoid is cortisol or dexamethasone.
- 38. A method for decreasing apoptosis of bone cells in a mammal that comprises administering to the mammal a siRNA comprising SEQ ID NO: 11, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 35, SEQ ID NO: 38, SEQ ID NO: 41 or SEQ ID NO: 44, wherein the siRNA can modulate SOST expression.
- 39. A method for decreasing apoptosis of bone cells in a mammal that comprises administering to the mammal a siRNA that is selectively hybridizable under stringent conditions to an RNA derived from a DNA comprising SEQ ID NO: 9, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 18, SEQ ID NO: 21, SEQ ID NO: 24, SEQ ID NO: 27, SEQ ID NO: 30, SEQ ID NO: 33, SEQ ID NO: 36, SEQ ID NO: 39, or SEQ ID NO: 42, wherein the siRNA can modulate SOST expression.
- 40. A method for identifying a factor that decreases SOST expression comprising:
(1) providing a cell that comprises a nucleic acid construct comprising a SOST promoter comprising SEQ ID NO: 4 that is operably linked to a nucleic acid encoding a detectable marker; (2) contacting the cell with a test agent; and (3) detecting whether the test agent decreases expression of the detectable marker relative to a control that comprises a cell that has not been contacted with a test agent.
- 41. The method of claim 40, wherein the cell is responsive to a bone morphogenetic protein.
- 42. The method of claim 40, wherein the cell is a C2C12 cell from a cell line having ATCC Deposit No. CRL-1772 or a C3H10T1/2 cell from a cell line having ATCC Deposit No. CCL-226.
- 43. The method of claim 40, wherein the cell is a human mesenchymal (hMSC) cell.
- 44. The method of claim 40, wherein the nucleic acid construct further comprises a nucleic acid segment encoding an osteoblastic-specific steroid response element.
- 45. The method of claim 40, wherein the nucleic acid construct further comprises a nucleic acid segment encoding glucocorticoid response element.
- 46. A method for identifying a factor that decreases SOST expression comprising:
(1) contacting a cell with a test agent; and (2) detecting whether endogenous SOST expression decreases, wherein the cell comprises a nucleic acid encoding a protein comprising SEQ ID NO: 3 or SEQ ID NO: 6 or SEQ ID NO: 8.
- 47. The method of claim 46, wherein the nucleic acid comprises SEQ ID NO: 1 or SEQ ID NO: 2 or SEQ ID NO: 5 or SEQ ID NO: 7.
- 48. A method for identifying an antagonist for sclerostin comprising:
(1) contacting a cell with sclerostin and a test agent; and (2) detecting whether the test agent prevents apoptosis of the cell.
- 49. A method for identifying a molecule that binds to sclerostin comprising:
(1) contacting a test agent with a sclerostin polypeptide comprising SEQ ID NO: 3 or SEQ ID NO: 6 or SEQ ID NO: 8; and (2) determining whether the test agent binds to the polypeptide.
- 50. A marker for osteoblast differentiation comprising a sclerostin polypeptide comprising SEQ ID NO: 3 or SEQ ID NO: 6 or SEQ ID NO: 8.
- 51. A marker for osteoblast differentiation comprising a nucleic acid comprising SEQ ID NO: 1 or SEQ ID NO: 2 or SEQ ID NO: 5 or SEQ ID NO: 7.
Parent Case Info
[0001] This application claims priority from U.S. application Ser. No. 60/361,258 filed Mar. 1, 2002, from. U.S. application Ser. No. 60/406,171 filed Aug. 27, 2002 and from U.S. application Ser. No. ______ filed Feb. 13, 2003.
Provisional Applications (3)
|
Number |
Date |
Country |
|
60361258 |
Mar 2002 |
US |
|
60406171 |
Aug 2002 |
US |
|
60447393 |
Feb 2003 |
US |