Methods and means for treatment of osteoarthritis
The invention relates to the field of medicinal research, cartilage physiology and diseases involving the degeneration of cartilage tissue. More specifically, the invention relates to methods and means for identifying compounds that inhibit catabolic processes in chondrocytes and that decrease the degradation of cartilage and/or ECM. The invention also relates to the compounds that are useful in the treatment of osteoarthritis. The invention also relates to targets, the modulation of which results in a decrease in the degradation of ECM and/or cartilage and decrease inflammation. In addition, the invention relates to compositions and methods for the use thereof in treating conditions that are characterized by the degradation of ECM and/or cartilage and inflammation.
1. A method for identifying a compound that inhibits type II collagen degradation in extracellular matrix (ECM) and/or cartilage, comprising:
(a) contacting a compound with a polypeptide comprising the amino acid sequence of SEQ ID NO: 29;
(b) selecting a compound that binds said polypeptide; and
(c) measuring the ability of the compound selected in (b) to inhibit expression and/or activity of matrix metalloproteinase 13 (MMP13).
2. The method according to claim 1 , wherein said polypeptide is in an in vitro cell-free preparation.
3. The method according to claim 1 , wherein said polypeptide is present in a mammalian cell.
4. The method of claim 1 , wherein the method is used to identify compounds that inhibit the catabolic process of chondrocytes.
5. The method of claim 1 , which comprises the steps of:
c) contacting a population of mammalian cells expressing said polypeptide with one or more compound that exhibits a binding affinity for said polypeptide; and
d) identifying a compound that inhibits expression and/or activity of MMP13 as a compound that inhibits type II collagen degradation in ECM and/or cartilage.
6. The method of claim 1 or 5 , wherein the compound that binds said polypeptide has a binding affinity to the polypeptide of at least 10 micromolar.
7. The method according to claim 1 , which additionally comprises the step of comparing the compound to be tested to a control.
8. The method according to claim 7 , wherein said control is where the polypeptide has not been contacted with said compound.
9. The method according to claim 5 , which additionally comprises the step of comparing the compound to a control, wherein said control is a population of mammalian cells that does not express said polypeptide.
10. The method according to claim 1 or 5 , wherein said compound is selected from the group consisting of compounds of a commercially available screening library and compounds having binding affinity for a polypeptide comprising the amino acid sequence of SEQ ID NO: 29.
11. The method according to claim 1 , wherein said compound is a peptide in a phage display library or an antibody fragment library.