LDL Receptor-Related Proteins 1 and 2 and Treatment of Bone or Cartilage Conditions

Abstract

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.