Method of diagnosing adolescent idiopathic scoliosis

Abstract

A method for diagnosing an increased risk for developing adolescent idiopathic scoliosis (AIS) in a human subject, comprising detecting the presence or absence of at least one impairment in melatonin-signaling pathway in a cell sample of the subject in the presence and in the absence of a known melatonin-signaling pathway agonist, wherein the cell sample is selected from the group consisting of blood cell sample, osteoblast cell sample, osteoclast cell sample and myoblast cell sample, and wherein the presence of the at least one impairment in the melatonin-signaling pathway indicates that the subject possesses an increased risk for developing AIS.

1 . A method for diagnosing an increased risk for developing adolescent idiopathic scoliosis (AIS) in a human subject, comprising detecting the presence or absence of at least one impairment in melatonin-signaling pathway in a cell sample of the subject in the presence and in the absence of a known melatonin-signaling pathway agonist, wherein the cell sample is selected from the group consisting of blood cell sample, osteoblast cell sample, osteoclast cell sample and myoblast cell sample, and wherein the presence of the at least one impairment in the melatonin-signaling pathway indicates that the subject possesses an increased risk for developing AIS. 
     
     
         2 . The method of  claim 1 , wherein said cell sample is a blood cell sample selected from the group consisting of lymphocyte cell sample and monocyte cell sample. 
     
     
         3 . The method of  claim 1 , wherein said cell sample is a lymphocyte cell sample. 
     
     
         4 . The method of  claim 1 , wherein said cell sample is a monocyte cell sample. 
     
     
         5 . The method of  claim 1 , wherein said known melatonin-signaling pathway agonist is melatonin or an analog thereof. 
     
     
         6 . The method of  claim 1 , wherein said known melatonin-signaling pathway agonist is melatonin. 
     
     
         7 . The method of  claim 1 , wherein said known melatonin-signaling pathway agonist is GTP or an analog thereof. 
     
     
         8 . The method of  claim 1 , wherein said known melatonin-signaling pathway agonist is GTP. 
     
     
         9 . The method of  claim 1 , wherein said at least one impairment is detected by an accumulation of cyclic adenosine 5′-monophosphate (cAMP) in said cell sample as compared to that in a control cell sample. 
     
     
         10 . The method of  claim 9 , wherein said accumulation of cAMP is induced by a known activator of adenylyl cyclase. 
     
     
         11 . The method of  claim 10 , wherein said known activator of adenylyl cyclase is forskolin. 
     
     
         12 . The method of  claim 9 , wherein said accumulation of cAMP is induced by a known activator of adenylyl cyclase, and the impairment is detected by an absence of inhibition of said accumulation in the presence of the known melatonin-signaling pathway agonist. 
     
     
         13 . The method of  claim 12 , wherein said known activator of adenylyl cyclase is forskolin. 
     
     
         14 . The method of  claim 9 , wherein said accumulation of cAMP is induced by a known activator of adenylyl cyclase, and the impairment is detected by a lower inhibition of said accumulation in the presence of the known melatonin-signaling pathway agonist in the cell sample as compared to that in a control cell sample. 
     
     
         15 . The method of  claim 14 , wherein said known activator of adenylyl cyclase is forskolin. 
     
     
         16 . The method of  claim 9 , wherein said accumulation of cAMP is induced by a known activator of adenylyl cyclase, and wherein inhibition of said accumulation by the known melatonin-signaling pathway agonist is detectably reduced in the cell sample as compared to that in a control cell sample. 
     
     
         17 . The method of  claim 16 , wherein said known activator of adenylyl cyclase is forskolin. 
     
     
         18 . The method of  claim 1 , wherein said at least one impairment is detected by a reduction of inhibition of osteoclast resorption activity in the presence of the known melatonin-signaling pathway agonist. 
     
     
         19 . The method of  claim 1 , wherein said impairment is detected by an absence of proliferation of at least one of said cells in the presence of the known melatonin-signaling pathway agonist. 
     
     
         20 . The method of  claim 1 , further comprising a step of selecting a treatment for the subject based on the results of the detecting step.