Methods and compositions for treating metabolic bone diseases relating to human endokine alpha
The present invention concerns methods for diagnosis and treatment of metabolic bone diseases and disorders using a novel member of the tumor necrosis factor (TNF) family of cytokines. In particular the invention provides methods of using the Endokine alpha protein and/or homomultimeric and/or heteromultimeric polypeptide complexes containing Endokine alpha, in the diagnosis, prognosis and treatment of metabolic bone diseases and disorders. Also provided by the invention are methods of using the Endokine alpha protein and/or homomultimeric and/or heteromultimeric polypeptide complexes containing Endokine alpha, in the diagnosis, prognosis and treatment of diseases and/or disorders associated with aberrant osteoclast development and/or activity. The present invention also provides isolated polynucleotides encoding polypeptides of the invention, antibodies thereto, and agonists and antagonists thereof, for use in the diagnosis, prognosis and treatment of metabolic bone diseases and disorders.
1. A method of treating an individual having a disorder associated with excessive bone resorption, comprising administering to the individual a therapeutically effective amount of a composition comprising an isolated Endokine alpha polypeptide having an amino acid sequence selected from the group consisting of:
(a) amino acids 1 to 169 of SEQ ID NO:40;
(b) amino acids 2 to 169 of SEQ ID NO:40;
(c) amino acids 44 to 169 of SEQ ID NO:40; and
(d) the amino acid sequence of the Endokine alpha polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97640.
2. The method of claim 1 wherein said amino acid sequence is (a).
3. The method of claim 1 wherein said amino acid sequence is (b).
4. The method of claim 1 wherein said amino acid sequence is (c).
5. The method of claim 1 wherein said amino acid sequence is (d).
6. The method of claim 1 wherein said Endokine alpha polypeptide further comprises an epitope tag.
7. The method of claim 1 wherein the disorder is osteoporosis.
8. The method of claim 1 wherein the disorder is Paget's disease.
9. The method of claim 1 wherein the disorder is arterial calcification.
10. A method of inhibiting RANK expression in a monocyte, macrophage, or osteoclast cell, comprising contacting the cell with an effective amount of a composition comprising an isolated Endokine alpha polypeptide having an amino acid sequence selected from the group consisting of:
(a) amino acids 1 to 169 of SEQ ID NQ:40;
(b) amino acids 2 to 169 of SEQ ID NO:40;
(C) amino acids 44 to 169 of SEQ ID NO:40; and
(d) the amino acid sequence of the Endokine alpha polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97640.
11. The method of claim 10 wherein the cell is contacted in vivo.
12. The method of claim 10 wherein the cell is contacted in vitro.
13. A method of increasing TNF alpha production in a monocyte, macrophage, or osteoclast cell, comprising contacting the cell with an effective amount of a composition comprising an isolated Endokine alpha polypeptide having an amino acid sequence selected from the group consisting of:
(a) ammo acids 1 to 169 of SEQ ID NO:40;
(b) amino acids 2 to 169 of SEQ ID NO:40;
(c) amino acids 44 to 169 of SEQ ID NO:40; and
(d) the amino acid sequence of the Endokine alpha polypeptide having the amino acid sequence encoded by the cDNA clone contained in ATCC Deposit No. 97640.
14. The method of claim 13 wherein the cell is contacted in vivo.
15. The method of claim 13 wherein the cell is contacted in vitro.
16. A method of treating an individual having a disorder associated wit excessive bone resorption, comprising administering to the individual a therapeutically effective amount of a composition comprising an Endokine alpha fusion protein, said fusion protein consisting of amino acids 39 to 169 of SEQ ID NO:40 fused to an epitope tag.
17. The method of claim 16 wherein the disorder is osteoporosis.
18. The method of claim 16 wherein the disorder is Paget's disease.
19. The method of claim 16 wherein the disorder is arterial calcification.
20. A method of inhibiting RANK expression in a monocyte, macrophage, or osteoclast cell, comprising contacting the cell with an effective amount of a composition comprising an Endokine alpha fusion protein, said fusion protein consisting of amino acids 39 to 169 of SEQ ID NO:40 fused to an epitope tag.
21. The method of claim 20 wherein the cell is contacted in vivo.
22. The method of claim 20 wherein the cell is contacted in vitro.
23. A method of increasing TNF alpha production in a monocyte, macrophage, or osteoclast cell, comprising contacting the cell with an effective amount of a composition comprising an Endokine alpha fusion protein, said fusion protein consisting of amino acids 39 to 169 of SEQ ID NO:40 fused to an epitope tag.
24. The method of claim 23 wherein the cell is contacted in vivo.
25. The method of claim 23 wherein the cell is contacted in vitro.