Stimulation of bone growth with thrombin peptide derivatives
Disclosed is a method of stimulating bone growth at a site in a subject in need of osteoinduction. The method comprises the step of administering a therapeutically effective amount of an agonist of the non-proteolytically activated thrombin receptor to the site.
1. A method for inducing bone growth to produce a spinal fusion in a subject, said method comprising administering to one or more sites between vertebrae a therapeutically effective amount of a peptide of between 12 and 23 amino acids in length represented by the following structural formula:
Arg-Gly-Asp-Ala-R,
wherein Asp-Ala-R is a serine esterase conserved sequence.
2. The method of claim 1 , wherein the peptide is 23 amino acids in length.
3. The method of claim 1 , wherein R comprises the amino acid sequence Cys-X 1 -Gly-Asp-Ser-Gly-Gly-Pro-X 2 -Val (SEQ ID NO: 2), wherein X 1 is Glu or Gln and X 2 is Phe, Met, Leu, His or Val.
4. The method of claim 1 , wherein the peptide comprises the amino acid sequence Arg-Gly-Asp-Ala-Cys-X 1 -Gly-Asp-Ser-Gly-Gly-Pro-X 2 -Val (SEQ ID NO: 4), wherein X 1 is Glu or Gln and X 2 is Phe, Met, Leu, His or Val.
5. The method of claim 1 , wherein the peptide comprises a C-terminal amide.
6. The method of claim 1 , wherein the serine esterase conserved sequence comprises SEQ ID NO:1.
7. The method of claim 1 , wherein the peptide is administered in a pharmaceutical composition additionally comprising an implantable, biocompatible carrier.
8. The method of claim 7 , wherein the implantable, biocompatible carrier is an osteoconductive matrix.
9. The method of claim 7 , wherein the carrier comprises a polylactic acid/polyglycolic acid homopolymer or copolymer.
10. A method for inducing bone growth to produce a spinal fusion in a subject, said method comprising administering to one or more sites between vertebrae a therapeutically effective amount of a peptide consisting of the amino acid sequence Ala-Gly-Tyr-Lys-Pro-Asp-Glu-Gly-Lys-Arg-Gly-Asp-Cys-Glu-Gly-Asp-Ser-Gly-Gly-Pro-Phe-Val (SEQ ID NO: 5).
11. The method of claim 10 , wherein the subject is a human.
12. The method of claim 10 , wherein the subject is a farm animal, a companion animal or a laboratory animal.
13. A method for inducing bone growth to produce a spinal fusion in a subject, said method comprising administering to one or more sites between vertebrae a therapeutically effective amount of the peptide consisting of Ala-Gly-Tyr-Lys-Pro-Asp-Glu-Gly-Lys-Arg-Gly-Asp-Ala-Cys-Glu-Gly-Asp-Ser-Gly-Gly-Pro-Phe-Val (SEQ ID NO: 6).
14. The method of claim 13 , wherein the peptide is administered in a pharmaceutical composition additionally comprising an implantable, biocompatible carrier.
15. The method of claim 13 , wherein the implantable, biocompatible carrier is an osteoconductive matrix.
16. The method of claim 13 , wherein the carrier comprises a polylactic acid/polyglycolic acid homopolymer or copolymer.
17. A method for inducing bone growth to produce a spinal fusion in a subject, said method comprising administering to one or more sites between vertebrae a therapeutically effective amount of the peptide consisting of Ala-Gly-Tyr-Lys-Pro-Asp-Glu-Gly-Lys-Arg-Gly-Asp-Ala-Cys-Glu-Gly-Asp-Ser-Gly-Gly-Pro-Phe-Val-NH 2 (SEQ ID NO: 7).
18. The method of claim 17 wherein the peptide is administered in a pharmaceutical composition by injection.
19. The method of claim 17 wherein the peptide is administered in conjunction with an implantable prosthetic device.
20. The method of claim 17 , wherein the peptide is administered in a pharmaceutical composition additionally comprising an implantable, biocompatible carrier.
21. The method of claim 17 , wherein the implantable, biocompatible carrier is an osteoconductive matrix.
22. The method of claim 17 , wherein the carrier comprises a polylactic acid/polyglycolic acid homopolymer or copolymer.