Mesenchymal stem cell differentiation
The present invention provides for methods and compositions for treating or preventing arthritis and joint injury.
1. A polypeptide consisting of an amino acid sequence as set forth in any one of SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7, wherein said polypeptide is PEGylated.
2. The polypeptide of claim 1 , which has chondrogenic activity.
3. The polypeptide of claim 1 , wherein the polypeptide has chondrogenic activity and reduced glycosylation relative to a naturally-occurring human Angiopoietin-like 3 (ANGPTL3).
4. A pharmaceutical composition comprising an effective amount of the polypeptide of claim 1 .
5. The pharmaceutical composition of claim 4 , further comprising a buffer.
6. The pharmaceutical composition of claim 4 , further comprising hyaluronic acid.
7. The pharmaceutical composition of claim 4 , wherein the pharmaceutical composition is suitable for intra-articular delivery.
8. The pharmaceutical composition of claim 4 , further comprising a preservative.
9. A fusion protein comprising a polypeptide consisting of an amino acid sequence as set forth in any one of SEQ ID NO:5, SEQ ID NO:6, or SEQ ID NO:7 fused to a human serum albumin (HSA), an immunoglobulin heavy chain constant region (Fc), a polyhistidine, a glutathione S transferase (GST), a thioredoxin, a protein A, a protein G, or a maltose binding protein (MBP).
10. The fusion protein of claim 9 , wherein the fusion protein is PEGylated.
11. The fusion protein of claim 9 , wherein the polypeptide has chondrogenic activity.
12. The fusion protein of claim 9 , wherein the polypeptide has chondrogenic activity and reduced glycosylation relative to a naturally-occurring human ANGPTL3.
13. A pharmaceutical composition comprising an effective amount of the fusion protein of claim 9 .
14. The pharmaceutical composition of claim 13 , further comprising a buffer.
15. The pharmaceutical composition of claim 13 , further comprising hyaluronic acid.
16. The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition is suitable for intra-articular delivery.
17. The pharmaceutical composition of claim 13 , further comprising a preservative.
18. The pharmaceutical composition of claim 13 , wherein the pharmaceutical composition is suitable for intra-articular delivery.