IL-17 receptor-like protein, uses thereof, and modulation of catabolic activity of il-17 cytokines on bone and cartilage

A polypeptide with 85% or greater sequence identity to a polypeptide having a sequence selected from the group consisting of:

• SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:
• 11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, and SEQ ID NO:25, which polypeptide binds to an interleukin-17 (IL-17) selected from the group consisting of IL-17A, IL-17B, IL-17C, IL-17E and IL-17F.

A method of decreasing catabolic activity in bone or cartilage in a mammal, said method comprising administering to said mammal a polypeptide with 85% or greater sequence identity to a polypeptide having a sequence selected from the group consisting of:

• SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, and SEQ ID NO:25, which polypeptide binds to an interleukin-17 (IL-17) selected from the group consisting of IL-17A, IL-17B, IL-17C, IL-17E and IL-17F, in an amount sufficient to lower levels of said IL-17, thereby decreasing catabolic activity in said bone or cartilage.

A method of decreasing catabolic activity in bone or cartilage in a mammal, said method comprising administering to said mammal a polypeptide with 90% or greater sequence identity to a polypeptide having a sequence selected from the group consisting of:

• SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, and SEQ ID NO:25, which polypeptide binds to an interleukin-17 (IL-17) selected from the group consisting of IL-17A, IL-17B, IL-17C, IL-17E and IL-17F, in an amount sufficient to lower levels of said IL-17, thereby decreasing catabolic activity in said bone or cartilage.

A method of decreasing catabolic activity in bone or cartilage in a mammal, said method comprising administering to said mammal a polypeptide with 95% or greater sequence identity to a polypeptide having a sequence selected from the group consisting of:

• SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID) NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, and SEQ ID NO:25, which polypeptide binds to an interleukin-17 (IL-17) selected from the group consisting of IL-17A, IL-17B, IL-17C, IL-17E and IL-17F, in an amount sufficient to lower levels of free IL-17 in said mammal, thereby decreasing catabolic activity in said bone or cartilage.

A method of decreasing catabolic activity in bone or cartilage in a mammal, said method comprising administering to said mammal a polypeptide having a sequence selected from the group consisting of:

• SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, and SEQ ID NO:25, in an amount sufficient to lower levels of free IL-17 cytokines in said mammal, thereby decreasing catabolic activity in said bone or cartilage.

A method of determining the aggressiveness of a prostate cancer cell, said method comprising determining the presence or absence in said cell of an epitope of IL-17RL (SEQ ID NO:1), wherein the determination that said epitope is absent in said cell indicates that the cancer is more aggressive than a like cell in which said epitope is present.

A method of restoring androgen-responsiveness to a prostate cancer cell, said method comprising administering to said prostate cancer cell a nucleic acid encoding a polypeptide which binds IL-17B, and further wherein the polypeptide has 90% or greater sequence identity to a polypeptide having a sequence selected from the group consisting of:

• SEQ ID NO:2, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23 and SEQ ID NO:25, thereby restoring androgen-responsiveness to said prostate cancer cell.

A method of restoring androgen-responsiveness to a prostate cancer cell, said method comprising administering to said prostate cancer cell a nucleic acid encoding a polypeptide which binds IL-17B, and further wherein the polypeptide has 95% or greater sequence identity to a polypeptide having a sequence selected from the group consisting of:

• SEQ ID NO:2, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23 and SEQ ID NO:25, thereby restoring androgen-responsiveness to said prostate cancer cell.

A method of restoring androgen-responsiveness to a prostate cancer cell, said method comprising administering to said prostate cancer cell a nucleic acid encoding a polypeptide which binds IL-17B, and further wherein the polypeptide has a sequence selected from the group consisting of:

• SEQ ID NO:2, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23 and SEQ ID NO:25, thereby restoring androgen-responsiveness to said prostate cancer cell.

An antibody which binds to a polypeptide having a sequence selected from the group consisting of:

• SEQ ID NO:2, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, and SEQ ID NO:25.

A method of stimulating growth of bone or cartilage in a patient with a bone or cartilage pathology, the method comprising administering an IL-17B antagonist to the patient, thereby stimulating the growth of bone or cartilage.

A method of potentiating the activity of a bone morphogenetic protein in a mammal, the method comprising administering the bone morphogenetic protein and a IL-17B antagonist to the mammal.

A method of enhancing the regenerative potential of a tissue graft, comprising transforming cells of the tissue graft with an IL-17B antagonist.

A method of inhibiting ossification or calcification in a mammal suffering from pathological ossification or calcification, the method comprising administering IL-17B to the mammal in an amount sufficient to inhibit ossification or calcification.

A method of diagnosing a cartilage degenerative disorder in a mammal, comprising the steps of:

• (a) obtaining a sample of tissue from the mammal
• (b) measuring the amount of IL-17B in the sample, and
• (c) comparing the amount of IL-17B in the sample with the amount of IL-17B in a sample of tissue from a mammal known to have a cartilage degenerative disorder.

A method of stimulating proteoglycan synthesis by a chondrocyte in culture, the method comprising contacting the chondrocyte with an IL-17B antagonist, such that the rate of proteoglycan synthesis is increased.

A method of inhibiting the rate of proteoglycan synthesis by a chondrocyte in culture, comprising the step of contacting the chondrocyte with IL-17B, such that the rate of proteoglycan synthesis is decreased.

A mammalian cell comprising a polynucleotide encoding an IL-17B antagonist, wherein the mammalian cell is selected from the group consisting of a chondrocyte, a synoviocyte, and a mesenchymal stem cell.

A composition comprising a cartilage growth factor and an IL-17B antagonist in a pharmaceutically acceptable carrier.

A composition comprising an IL-17B antagonist and an insoluble carrier matrix.

A use of an IL-17B antagonist selected from the group consisting of an antibody and IL-17RL for the manufacture of a medicament to stimulating growth of bone or cartilage in a patient with a bone or cartilage pathology.

A use of an IL-17RL for the manufacture of a medicament to potentiate the activity of a bone morphogenetic protein in a mammal.

A polypeptide encoded by at least one exon selected from the group consisting of exons 1 to 19 (SEQ ID NOs:55-73) of I17RL (SEQ ID NOs:1), which polypeptide binds to an interleukin-17 (IL-17) selected from the group consisting of IL-17A, IL-17B, IL-17C, IL-17E and IL-17F.

A polypeptide with at least 85% identity to SEQ ID NO:75, which polypeptide binds to an interleukin-17 (IL-17) selected from the group consisting of IL-17A, IL-17B, IL-17C, IL-17E and IL-17F.