LDL Receptor-Related Proteins 1 and 2 and Treatment of Bone or Cartilage Conditions
LDL receptor-related proteins 1 and 2 (LRP-1 and LRP-2) and interaction between lactoferrin and LRP-1, LRP-2, or p42/44 MAP kinase in diagnosis and treatment of disorders such as bone or cartilage disorders. Also disclosed are methods of screening for related therapeutic compounds.
1 . A method of determining whether a patient is suffering from or at risk for developing a bone condition, the method comprising:
providing a test sample from a patient suspected of suffering from or being at risk for developing a bone condition, and
quantifying an expression level of an LRP-1 gene,
wherein the expression level of the LRP-1 gene in the test sample, if different from that in a normal sample, indicates that the patient is suffering from or at risk for developing a bone condition.
2 . The method of claim 1 , wherein the test sample is prepared from a bone tissue.
3 . A method of determining whether a patient is suffering from or at risk for developing a bone condition, the method comprising:
providing a test sample from a patient suspected of suffering from or being at risk for developing a bone condition, and
quantifying an activity of an LRP-1 protein,
wherein the activity of the LRP-1 protein in the test sample, if different from that in a normal sample, indicates that the patient is suffering from or at risk for developing a bone condition.
4 . The method of claim 3 , wherein the test sample is prepared from a bone tissue.
5 . A method of identifying a candidate compound for treating a bone condition, the method comprising:
contacting a compound with a cell expressing an LRP-1 gene, and
quantifying an expression level of the LRP-1 gene in the cell,
wherein the expression level of the LRP-1 gene in the presence of the compound, if different from that in the absence of the compound, indicates that the compound is a candidate for treating a bone condition.
6 . The method of claim 5 , wherein the cell is an osteoblast cell, osteoblast-like cell, or osteocyte.
7 . The method of claim 6 , wherein the cell is a SaOS-2 cell.
8 . The method of claim 5 , wherein the cell is an osteoclast cell.
9 . A method of identifying a candidate compound for treating a bone condition, the method comprising:
contacting a compound with a cell expressing an LRP-1 gene encoding an LRP-1 protein, and
quantifying an activity of the LRP-1 protein in the cell,
wherein the activity of the LRP-1 protein in the presence of the compound, if different from that in the absence of the compound, indicates that the compound is a candidate for treating a bone condition.
10 . The method of claim 9 , wherein the cell is an osteoblast cell, osteoblast-like cell, or osteocyte.
11 . The method of claim 10 , wherein the cell is a SaOS-2 cell.
12 . The method of claim 9 , wherein the cell is an osteoclast cell.
13 . A method of treating a bone condition, the method comprising modulating a level of an LRP-1 protein in bone cells.
14 . The method of claim 13 , wherein the level of the LRP-1 protein is modulated by providing and expressing a nucleic acid encoding an LRP-1 protein.
15 . The method of claim 14 , wherein the nucleic acid is expressed in the bone cells.
16 . The method of claim 13 , wherein the level of the LRP-1 protein is modulated by providing an LRP-1 protein.
17 . The method of claim 16 , wherein the LRP-1 protein is introduced into the bone cells.
18 . The method of claim 13 , wherein the level of the LRP-1 protein is modulated by providing and expressing a nucleic acid complementary to a sequence encoding an LRP-1 protein.
19 . The method of claim 18 , wherein the nucleic acid is expressed in the bone cells.
20 . A method of treating a bone condition, the method comprising modulating an activity of an LRP-1 protein in bone cells.
21 . The method of claim 20 , wherein the activity of the LRP-1 protein is modulated by providing an agonist of the LRP-1 protein.
22 . The method of claim 21 , wherein the agonist is introduced into the bone cells.
23 . The method of claim 20 , wherein the activity of the LRP-1 protein is modulated by providing an antagonist of the LRP-1 protein.
24 . The method of claim 23 , wherein the antagonist is introduced into the bone cells.
25 . The method of claim 20 , wherein the activity of the LRP-1 protein is modulated by providing an antibody against the LRP-1 protein.
26 . The method of claim 25 , wherein the antibody is introduced into the bone cells.
27 . A method of determining whether a patient is suffering from or at risk for developing a bone condition, the method comprising:
providing a test sample from a bone tissue of a patient suspected of suffering from or being at risk for developing a bone condition, and
quantifying an expression level of an LRP-2 gene,
wherein the expression level of the LRP-2 gene in the test sample, if different from that in a normal sample, indicates that the patient is suffering from or at risk for developing a bone condition.
28 . A method of determining whether a patient is suffering from or at risk for developing a bone condition, the method comprising:
providing a test sample from a bone tissue of a patient suspected of suffering from or being at risk for developing a bone condition, and
quantifying an activity of an LRP-2 protein,
wherein the activity of the LRP-2 protein in the test sample, if different from that in a normal sample, indicates that the patient is suffering from or at risk for developing a bone condition.
29 . A method of identifying a candidate compound for treating a bone condition, the method comprising:
contacting a compound with a bone cell expressing an LRP-2 gene, and
quantifying an expression level of the LRP-2 gene in the cell,
wherein the expression level of the LRP-2 gene in the presence of the compound, if different from that in the absence of the compound, indicates that the compound is a candidate for treating a bone condition.
30 . The method of claim 29 , wherein the cell is an osteoblast cell, osteoblast-like cell, or osteocyte.
31 . The method of claim 30 , wherein the cell is a SaOS-2 cell.
32 . The method of claim 29 , wherein the cell is an osteoclast cell.
33 . A method of identifying a candidate compound for treating a bone condition, the method comprising:
contacting a compound with a bone cell expressing an LRP-2 gene encoding an LRP-2 protein, and
quantifying an activity of the LRP-2 protein in the cell,
wherein the activity of the LRP-2 protein in the presence of the compound, if different from that in the absence of the compound, indicates that the compound is a candidate for treating a bone condition.
34 . The method of claim 33 , wherein the cell is an osteoblast cell, osteoblast-like cell, or osteocyte.
35 . The method of claim 34 , wherein the cell is a SaOS-2 cell.
36 . The method of claim 33 , wherein the cell is an osteoclast cell.
37 . A method of treating a bone condition, the method comprising modulating a level of an LRP-2 protein in bone cells.
38 . The method of claim 37 , wherein the level of the LRP-2 protein is modulated by introducing into and expressing in the bone cells a nucleic acid encoding an LRP-2 protein.
39 . The method of claim 37 , wherein the level of the LRP-2 protein is modulated by introducing into the bone cells an LRP-2 protein.
40 . The method of claim 37 , wherein the level of the LRP-2 protein is modulated by introducing into and expressing in the bone cells a nucleic acid complementary to a sequence encoding an LRP-2 protein.
41 . A method of treating a bone condition, the method comprising modulating an activity of an LRP-2 protein in bone cells.
42 . The method of claim 41 , wherein the activity of the LRP-2 protein is modulated by introducing into the bone cells an agonist of the LRP-2 protein.
43 . The method of claim 41 , wherein the activity of the LRP-2 protein is modulated by introducing into the bone cells an antagonist of the LRP-2 protein.
44 . The method of claim 41 , wherein the activity of the LRP-2 protein is modulated by introducing into the bone cells an antibody against the LRP-2 protein.
45 . A method of determining whether a subject is suffering from or at risk for developing a bone or cartilage condition, the method comprising:
providing a test sample from a subject, and
determining a level of interaction between a lactoferrin polypeptide and an LRP-1 or LRP-2 protein in the test sample,
wherein the level of the interaction between the lactoferrin polypeptide and the LRP-1 or LRP-2 protein in the test sample, if different from that in a normal sample, indicates that the subject is suffering from or at risk for developing a bone or cartilage condition.
46 . The method of claim 45 , wherein the test sample is prepared from a bone or cartilage tissue.
47 . A method of identifying a candidate compound for treating a bone or cartilage condition, the method comprising:
introducing a compound to a system containing a lactoferrin polypeptide and an LRP-1 or LRP-2 protein, and
determining a level of interaction between the lactoferrin polypeptide and the LRP-1 or LRP-2 protein,
wherein the level of the interaction between the lactoferrin polypeptide and the LRP-1 or LRP-2 protein in the presence of the compound, if different from that in the absence of the compound, indicates that the compound is a candidate for treating a bone or cartilage condition.
48 . The method of claim 47 , wherein the sample contains an osteoblastic, osteoclastic or fibroblastic cell, or a chondrocyte.
49 . A method of treating a bone or cartilage condition, the method comprising modulating interaction between a lactoferrin polypeptide and an LRP-1 or LRP-2 protein in bone or cartilage cells.
50 . The method of claim 49 , wherein the interaction between the lactoferrin polypeptide and the LRP-1 or LRP-2 protein is modulated by providing an agonist of the LRP-1 or LRP-2 protein.
51 . The method of claim 50 , wherein the agonist is introduced into the bone or cartilage cells.
52 . The method of claim 50 , wherein the agonist is an exogenous lactoferrin polypeptide.
53 . The method of claim 52 , wherein the exogenous lactoferrin polypeptide is introduced into the bone or cartilage cells.
54 . The method of claim 49 , wherein the interaction between the lactoferrin polypeptide and the LRP-1 or LRP-2 protein is modulated by providing an antagonist of the LRP-1 or LRP-2 protein.
55 . The method of claim 54 , wherein the antagonist is introduced into the bone or cartilage cells.
56 . The method of claim 54 , wherein the antagonist is a receptor-associated protein.
57 . The method of claim 56 , wherein the receptor-associated protein is introduced into the bone or cartilage cells.
58 . A method of determining whether a subject is suffering from or at risk for developing a bone or cartilage condition, the method comprising:
providing a test sample from a subject, and
determining a level of interaction between a lactoferrin polypeptide and a p42/44 MAP kinase in the test sample,
wherein the level of the interaction between the lactoferrin polypeptide and the p42/44 MAP kinase in the test sample, if different from that in a normal sample, indicates that the subject is suffering from or at risk for developing a bone or cartilage condition.
59 . The method of claim 58 , wherein the test sample is prepared from a bone or cartilage tissue.
60 . A method of identifying a candidate compound for treating a bone or cartilage condition, the method comprising:
introducing a compound with a system containing a lactoferrin polypeptide and a p42/44 MAP kinase, and
determining a level of interaction between the lactoferrin polypeptide and the p42/44 MAP kinase,
wherein the level of the interaction between the lactoferrin polypeptide and the p42/44 MAP kinase in the presence of the compound, if different from that in the absence of the compound, indicates that the compound is a candidate for treating a bone or cartilage condition.
61 . The method of claim 60 , wherein the sample contains an osteoblastic, osteoclastic or fibroblastic cell, or a chondrocyte.
62 . A method of treating a bone or cartilage condition, the method comprising modulating interaction between a lactoferrin polypeptide and a p42/44 MAP kinase in bone or cartilage cells.
63 . The method of claim 62 , wherein the interaction between the lactoferrin polypeptide and the p42/44 MAP kinase is modulated by providing an agonist of the p42/44 MAP kinase.
64 . The method of claim 63 , wherein the agonist is introduced into the bone or cartilage cells.
65 . The method of claim 63 , wherein the agonist is an exogenous lactoferrin polypeptide.
66 . The method of claim 65 , wherein the exogenous lactoferrin polypeptide is introduced into the bone or cartilage cells.
67 . The method of claim 62 , wherein the interaction between the lactoferrin polypeptide and the p42/44 MAP kinase is modulated by providing an antagonist of the p42/44 MAP kinase.
68 . The method of claim 67 , wherein the antagonist is introduced into the bone or cartilage cells.
69 . The method of claim 67 , wherein the antagonist is an inhibitor of a p42/44 MAP kinase.
70 . The method of claim 69 , wherein the inhibitor of the p42/44 MAP kinase is introduced into the bone or cartilage cells.