Compositions and methods for increasing bone mineralization

1. An isolated nucleic acid molecule comprising a polynucleotide sequence selected from the group consisting of:

(a) polynucleotide sequences that hybridize to the full complement of SEQ ID NO: 1, under conditions of high stringency comprising hybridization in 5×SSPE, 5×Denhardt's solution and 0.5% SDS overnight at 55 to 60° C.; followed by a post hybridization wash at 0.5×SSC at 55-60° C.;

(b) polynucleotide sequences having at least 85% sequence identity to SEQ ID NO: 1;

(c) polynucleotide sequences that encode a polypeptide having at least 85% sequence identity to SEQ ID NO: 2;

(d) nucleotides 119-686 of SEQ ID NO: 1;

(e) polynucleotide sequences having at least 85% sequence identity to nucleotides 119-686 of SEQ ID NO: 1;

(f) polynucleotide sequences that encode amino acids 25-213 of SEQ ID NO: 2; and

(g) polynucleotide sequences that encode a polypeptide having at least 85% sequence identity to amino acids 25-213 of SEQ ID NO: 2,

wherein the isolated nucleic acid molecule encodes a polypeptide that retains the biological activity of SEQ ID NO: 2 in regulating bone mineral content.

2. The isolated nucleic acid molecule according to claim 1 , which comprises a polynucleotide sequence that hybridizes to the full complement of SEQ NO: 1, under conditions of high stringency comprising hybridization in 5×SSPE, 5×Denhardt's solution and 0.5% SDS overnight at 55 to 60° C., followed by a post hybridization wash at 0.5×SSC at 55-60° C.

3. The nucleic acid molecule of claim 2 which is a primer, oligonucleotide, ribozyme or antisense oligonucleotide.

4. A composition comprising (a) a nucleic acid molecule of claim 3 and (b) a pharmaceutically acceptable carrier, excipient or diluent.

5. The isolated nucleic acid molecule according to claim 1 , which comprises a polynucleotide that encodes a polypeptide comprising amino acids 25-213 of SEQ ID NO: 2.

6. The isolated nucleic acid molecule according to claim 1 , which comprises a polynucleotide that encodes a polypeptide having at least 85% sequence identity to SEQ ID NO: 2.

7. A composition comprising (a) a nucleic acid molecule of claim 1 and (b) a pharmaceutically acceptable carrier, excipient or diluent.

8. A vector comprising an isolated nucleic acid molecule operably linked to a regulatory sequence that controls transcriptional expression, wherein said nucleic acid molecule comprises a polynucleotide sequence selected from the group consisting of:

(a) polynucleotide sequences that specifically hybridize to the full complement of SEQ ID NO: 1, under conditions of high stringency comprising hybridization in 5×SSPE, 5×Denhardt's solution and 0.5% SDS overnight at 55 to 60° C.; followed by a post hybridization wash at 0.5×SSC at 55-60° C.;

(b) polynucleotide sequences having at least 85% sequence identity to SEQ ID NO: 1;

(c) polynucleotide sequences that encode a polypeptide having at least 85% sequence identity to SEQ ID NO: 2;

(d) nucleotides 119-686 of SEQ ID NO: 1;

(e) polynucleotide sequences having at least 85% sequence identity to nucleotides 119-686 of SEQ ID NO: 1;

(f) polynucleotide sequences that encode amino acids 25-213 of SEQ ID NO: 2; and

(g) polynucleotide sequences that encode a polypeptide having at least 85% sequence identity to amino acids 25-213 of SEQ ID NO: 2,

wherein the isolated nucleic acid molecule encodes a polypeptide that retains the biological activity of SEQ ID NO: 2 in regulating bone mineral content.

9. The vector according to claim 8 , wherein the isolated nucleic acid molecule comprises a polynucleotide sequence that hybridizes to the full complement of SEQ ID NO: 1, under conditions of high stringency comprising hybridization in 5×SSPE, 5×Denhardt's solution and 0.5% SDS overnight at 55 to 60° C.; followed by a post hybridization wash at 0.5×SSC at 55-60° C.

10. The vector according to claim 8 , wherein the isolated nucleic acid molecule comprises a polynucleotide that encodes a polypeptide comprising amino acids 25-213 of SEQ ID NO: 2.

11. The vector according to claim 8 , wherein the isolated nucleic acid molecule comprises a polynucleotide that encodes a polypeptide having at least 85% sequence identity to SEQ ID NO: 2.

12. The vector according to claim 8 , wherein the isolated nucleic acid molecule comprises a polynucleotide that encodes a polypeptide having at least 85% sequence identity to amino acids 25-213 of SEQ ID NO: 2.

13. The vector according to claim 8 , wherein the regulatory sequence is a tissue-specific promoter.

14. The vector according to claim 8 , wherein the vector is a viral vector.

15. A host cell comprising a nucleic acid molecule operably linked to a heterologous regulatory sequence that controls transcriptional expression, wherein said nucleic acid molecule comprises a polynucleotide sequence selected from the group consisting of:

(a) SEQ ID NO: 1;

(b) polynucleotide sequences that specifically hybridize to the full complement of SEQ ID NO: 1, under conditions of high stringency comprising hybridization in 5×SSPE, 5×Denhardt's solution and 0.5% SDS overnight at 55 to 60° C.; followed by a post hybridization wash at 0.5×SSC at 55-60° C.;

(c) polynucleotide sequences having at least 85% sequence identity to SEQ ID NO: 1;

(d) polynucleotide sequences that encode SEQ ID NO: 2;

(e) polynucleotide sequences that encode a polypeptide having at least 85% sequence identity to SEQ ID NO: 2;

(f) nucleotides 119-686 of SEQ ID NO: 1;

(g) polynucleotide sequences having at least 85% sequence identity to nucleotides 119-686 of SEQ ID NO: 1;

(h) polynucleotide sequences that encode amino acids 25-213 of SEQ ID NO: 2; and

(i) polynucleotide sequences that encode a polypeptide having at least 85% sequence identity to amino acids 25-213 of SEQ ID NO: 2,

wherein the isolated nucleic acid molecule encodes a polypeptide that retains the biological activity of SEQ ID NO: 2 in regulating bone mineral content.

16. The host cell according to claim 15 , wherein the nucleic acid molecule comprises a polynucleotide sequence that specifically hybridizes to the full complement of SEQ ID NO: 1, under conditions of high stringency comprising hybridization in 5×SSPE, 5×Denhardt's solution and 0.5% SDS overnight at 55 to 60° C.; followed by a post hybridization wash at 0.5×SSC at 55-60° C.

17. The host cell according to claim 15 , wherein the nucleic acid molecule comprises a polynucleotide that encodes a polypeptide comprising amino acids 25-213 of SEQ ID NO: 2.

18. A method of making a polypeptide that retains the biological activity of a SEQ ID NO: 2 in regulating bone mineral content comprising (a) culturing the host cell according to claim 17 under conditions and for a time sufficient to produce said polypeptide, and (b) isolating said polypeptide.

19. The host cell according to claim 15 , wherein the nucleic acid molecule comprises a polynucleotide that encodes a polypeptide having at least 85% sequence identity to SEQ ID NO: 2.

20. The host cell according to claim 15 , wherein the nucleic acid molecule comprises nucleotides 119-686 of SEQ ID NO: 1.

21. The host cell according to claim 15 , wherein the nucleic acid molecule comprises a polynucleotide that encodes a polypeptide having at least 85% sequence identity to amino acids 25-213 of SEQ ID NO: 2.

22. A method of making a polypeptide that regulates bone mineral content comprising (a) culturing the host cell according to claim 5 under conditions and for a time sufficient to produce said polypeptide, and (b) isolating said polypeptide.

23. A host cell comprising a nucleic acid molecule operably linked to a heterologous regulatory sequence that controls transcriptional expression, wherein said nucleic acid molecule encodes a polypeptide comprising amino acids 25-213 of SEQ ID NO: 2.

24. A method of making a polypeptide that retains the biological activity of a SEQ ID NO: 2 in regulating bone mineral content comprising (a) culturing the host cell according to claim 23 under conditions and for a time sufficient to produce said polypeptide, and (b) isolating said polypeptide.