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 or quantifying an activity of an LRP-1 protein,
wherein the expression level of the LRP-1 gene or 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.
2 . The method of claim 1 , wherein the test sample is prepared from a bone tissue.
3 . A method of treating a bone condition, the method comprising modulating a level of an LRP-1 protein in bone cells or modulating an activity of an LRP-1 protein in bone cells.
4 . The method of claim 3 , wherein the level of the LRP-1 protein is modulated by providing and expressing a nucleic acid encoding an LRP-1 protein.
5 . The method of claim 4 , wherein the nucleic acid is expressed in the bone cells.
6 . The method of claim 3 , wherein the level of the LRP-1 protein is modulated by providing an LRP-1 protein.
7 . The method of claim 6 , wherein the LRP-1 protein is introduced into the bone cells.
8 . The method of claim 3 , 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.
9 . The method of claim 8 , wherein the nucleic acid is expressed in the bone cells.
10 . (canceled)
11 . The method of claim 3 , wherein the activity of the LRP-1 protein is modulated by providing an agonist of the LRP-1 protein.
12 . The method of claim 10 , wherein the agonist is introduced into the bone cells.
13 - 20 . (canceled)
21 . The method of claim 3 , wherein the activity of the LRP-1 protein is modulated by providing an agonist of the LRP-1protein.
22 . The method of claim 21 , wherein the agonist is introduced into the bone cells.
23 - 24 . (canceled)
25 . The method of claim 3 , 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 - 70 . (canceled)
71 . A method of treating a bone disorder, the method comprising administering an effective amount of a lactoferrin N-lobe polypeptide or a lactoferricin to a subject suffering from the bone disorder.
72 . The method of claim 71 , wherein the subject is in need of increased bone formation.
73 . The method of claim 71 , wherein the subject is in need of decreased bone resorption.
74 . The method of claim 71 , wherein the lactoferrin N-lobe polypeptide contains a metal ion.
75 . The method of claim 71 , wherein the lactoferrin N-lobe polypeptide contains an iron ion, copper ion, chromium ion, cobalt ion, manganese ion, zinc ion, or magnesium ion.
76 . The method of claim 71 , wherein the bone disorder is osteoporosis, rheumatoid or osteo-arthritis, hepatic osteodystrophy, osteomalacia, rickets, osteitis fibrosa cystica, renal osteodystrophy, osteosclerosis, osteopenia, fibrogenesis-imperfecta ossium, secondary hyperparathyrodism, hypoparathyroidism, hyperparathyroidism, chronic renal disease, sarcoidosis, glucocorticoid-induced osteoporosis, idiopathic hypercalcemia, Paget's disease, or osteogenesis imperfecta.
77 . The method of claim 71 , wherein the lactoferrin N-lobe polypeptide is administered locally.
78 . The method of claim 71 , wherein the lactoferrin N-lobe polypeptide is from human lactoferrin or bovine lactoferrin.
79 . The method of claim 71 , wherein the lactoferrin is from human lactoferrin or bovine lactoferrin.