Methods and compositions for regulating bone and cartilage formation

Abstract

The invention provides methods and compositions for diagnostic assays for detecting bone and cartilage formation and therapeutic methods and compositions for treating disease and disorders related to bone and cartilage formation or resorption, such as osteoporosis and bone fractions. The invention also provides therapeutic methods for diseases related to bone or cartilage formation or resorption. Methods for identifying therapeutics for such diseases are also provided.

1 - 65 . (canceled) 
     
     
         66 . A method for assessing the efficacy of a treatment for a disease associated with bone or cartilage metabolism in a subject comprising the steps of:
 determining the level or levels of gene expression of CRLF-1 and/or MMP23 in a first biological sample from the subject at a time point prior to treatment;   determining the corresponding level or levels of gene expression of CRLF-1 and/or MMP23 in a second biological sample from the subject at a time point after initiation of treatment; and   comparing the level or levels of gene expression of CRLF-1 and/or MMP23 in the first biological sample with the corresponding level or levels of gene expression of CRLF-1 and/or MMP23 in the second biological sample,   wherein a significant difference between the level or levels of gene expression of CRLF-1 and/or MMP23 in the first and second biological samples indicates that the treatment for the disease is efficacious.   
     
     
         67 . The method of  claim 66 , wherein the disease is associated with bone or cartilage formation. 
     
     
         68 . The method of  claim 66 , wherein the disease is associated with bone or cartilage resorption. 
     
     
         69 . The method of  claim 68 , wherein the treatment comprises administration of BMP-2. 
     
     
         70 . A method for monitoring a treatment for a disease associated with bone or cartilage metabolism in a subject comprising the steps of:
 determining the level or levels of gene expression of CRLF-1 and/or MMP23 in a first biological sample from the subject at a time point after initiation of treatment;   determining the corresponding level or levels of gene expression of CRLF-1 and/or MMP23 in a biological sample or samples from the subject at a later time point or points; and   comparing the level or levels of gene expression of CRLF-1 and/or MMP23 in the first biological sample with the corresponding level or levels of gene expression of CRLF-1 and/or MMP23 in the later biological sample or samples,   wherein the comparison between the level or levels of gene expression of CRLF-1 and/or MMP23 in the first biological sample and the later biological sample or samples is an indication of the efficacy of the treatment for the disease.   
     
     
         71 . The method of  claim 70 , wherein the disease is associated with bone or cartilage formation. 
     
     
         72 . The method of  claim 70 , wherein the disease is associated with bone or cartilage resorption. 
     
     
         73 . The method of  claim 72 , wherein the treatment comprises administration of BMP-2. 
     
     
         74 . A method for identifying a compound which stimulates bone or cartilage formation comprising the steps of:
 determining the level or levels of gene expression of CRLF-1 and/or MMP23 in a precursor cell population contacted with a test compound; and   comparing the level or levels of gene expression of CRLF-1 and/or MMP23 in the precursor cell population contacted with a test compound with the corresponding level or levels of gene expression of CRLF-1 and/or MMP23 in an uncontacted precursor cell population,   wherein a significant difference between the level or levels of gene expression of CRLF-1 and/or MMP23 in the two precursor cell populations indicates that the compound stimulates bone or cartilage formation.   
     
     
         75 . A method for identifying a compound which inhibits bone or cartilage formation comprising the steps of:
 determining the level or levels of gene expression of CRLF-1 and/or MMP23 in a precursor cell population contacted with a bone morphogenetic protein and a test compound; and   comparing the level or levels of gene expression of CRLF-1 and/or MMP23 in the precursor cell population contacted with the bone morphogenetic protein and the test compound with the corresponding level or levels of gene expression of CRLF-1 and/or MMP23 in a precursor cell population contacted only with the bone morphogenetic protein,   wherein a significant difference between the level or levels of gene expression of CRLF-1 and/or MMP23 in the two precursor cell populations indicates that the compound inhibits bone or cartilage formation.   
     
     
         76 . A method for treating a disease associated with bone or cartilage metabolism in a subject comprising administering to the subject one or more compounds that increases the expression and/or activity of CRLF-1 and/or MMP23. 
     
     
         77 . A method for treating a disease associated with bone or cartilage metabolism in a subject comprising administering to the subject one or more compounds that decreases the expression and/or activity of CRLF-1 and/or MMP23.