Tribonectins
The invention features a tribonectin and a method of tribosupplementation carried out by administering tribonectins directly to an injured or arthritic joint.
1. A method of reducing the coefficient of friction between tissue surfaces comprising administering a composition in an amount sufficient to lubricate a tissue surface, the composition comprising a tribonectin polypeptide comprising a lubricating polypeptide or a biologically active fragment thereof and an O-linked β(1-3) Gal-GalNAc oligosaccharide, the lubricating polypeptide or fragment comprising residues 200-1140 of sequence ID NO: 1 or a peptide mimetic thereof.
2. The method of claim 1 , wherein said tribonectin polypeptide comprises repeats of an amino acid sequence of sequence ID NO: 3.
3. The method of claim 2 , wherein said tribonectin polypeptide comprises fewer than 76 of said repeats.
4. The method of claim 1 , wherein said tribonectin polypeptide reduces the coefficient of friction between surfaces in vitro.
5. The method of claim 1 , wherein said tribonectin polypeptide reduces the coefficient of friction between bearing articular cartilage surfaces in vivo.
6. The method of claim 1 , wherein the molecular weight of said tribonectin polypeptide is in the range of 220-280 kDa.
7. The method of claim 1 , wherein said tribonectin polypeptide comprises a fragment of megakaryocyte stimulating factor.
8. The method of claim 1 , wherein said tribonectin polypeptide comprises an amino acid sequence that comprises a multiplicity of subunits comprising at least one glycosylated threonine.
9. The method of claim 1 , wherein said tribonectin polypeptide lacks the amino acid sequence of residues 1-24, inclusive, of SEQ ID NO: 1, or residues 67-104, inclusive, of SEQ ID NO: 1.
10. The method of claim 1 , further comprising administering to a bearing surface hyaluronic acid.
11. The method of claim 1 , wherein said tissue surfaces comprise bearing surfaces.
12. The method of claim 1 , comprising administering said composition to a human in a form suitable for the inhibition of tissue adhesion formation.
13. The method of claim 1 , comprising administering said composition to a human in an amount sufficient to lubricate bearing human tissue surfaces.
14. The method of claim 13 , comprising placing said composition between first and second human tissue surfaces having reduced lubrication.
15. The method of claim 1 , wherein said polypeptide lubricates an articulating joint of a human, dog, or horse.
16. The method of claim 1 , wherein said composition is in the form of a film, membrane, foam, gel or fiber.
17. The method of claim 1 , wherein said composition comprises a 20 to 500 μg/mL of said polypeptide.
18. The method of claim 17 , wherein said composition comprises 250 μg/mL of said polypeptide.
19. The method of claim 1 , wherein said composition is administered by injection.
20. A method of reducing the coefficient of friction between a tissue surface and an artificial device, comprising administering a composition in an amount sufficient to lubricate the tissue surface in contact with the artificial device, the composition comprising a tribonectin polypeptide comprising a lubricating polypeptide or a biologically active fragment thereof and an O-linked β(1-3) Gal-GalNAc oligosaccharide, the lubricating polypeptide or fragment comprising residues 200-1140 of sequence ID NO: 1 or a peptide mimetic thereof.