Abstract: The present invention provides a method of treating a subject in need thereof comprising classifying the subject into functional group FG1, FG2 or FG3, wherein i) when the subject is classified into the FG1 functional group, (A) the level of OPN or the activity of OPN in said subject is increased; (B) the subject is not treated with a brace; or (C) a combination of (A) and (B); and ii) when the subject is classified into the FG2 or FG3 functional group, (A) the level of OPN or the activity of OPN in said subject is decreased; (B) the subject is treated with a brace; or (C) a combination of (A) and (B).

Abstract: The present invention provides a method of treating a subject in need thereof comprising classifying the subject into functional group FG1, FG2 or FG3, wherein i) when the subject is classified into the FG1 functional group, (A) the level of OPN or the activity of OPN in said subject is increased; (B) the subject is not treated with a brace; or (C) a combination of (A) and (B); and ii) when the subject is classified into the FG2 or FG3 functional group, (A) the level of OPN or the activity of OPN in said subject is decreased; (B) the subject is treated with a brace; or (C) a combination of (A) and (B).

Abstract: Methods for diagnosing a predisposition to developing a scoliosis (e.g., adolescent idiopathic scoliosis (AIS)) and identifying compounds for treating scoliosis based on the modulation of Gi protein-coupled receptor activity are described. Specific embodiments of the methods involve measuring a change in impedance signals of cells expressing a receptor coupled to a Gi protein with a ligand. To identify compounds useful in treatment, the cell is contacted with a test compound and a ligand. A higher impedance in the presence relative to the absence of said test compound is indicative that the test compound is useful for treating scoliosis.

Abstract: A method of classifying a subject having idiopathic scoliosis (IS) or at risk of developing IS comprising: determining the cellular response to Gi stimulation in a cell sample from the subject in the presence of OPN; determining the cellular response to Gi stimulation in a cell sample from the subject in the absence of OPN; and comparing the cellular response obtained in the presence of OPN with the cellular response obtained in the absence of OPN, whereby the comparing step enables the classification of the subject into one IS functional group. Also provided is the use of the foregoing method to classify borderline subjects and kits for applying the methods.

Abstract: A method of classifying a subject having idiopathic scoliosis (IS) or at risk of developing IS comprising: determining the cellular response to Gi stimulation in a cell sample from the subject in the presence of OPN; determining the cellular response to Gi stimulation in a cell sample from the subject in the absence of OPN; and comparing the cellular response obtained in the presence of OPN with the cellular response obtained in the absence of OPN, whereby the comparing step enables the classification of the subject into one IS functional group. Also provided is the use of the foregoing method to classify borderline subjects and kits for applying the methods.

Abstract: Kits for stratifying a subject having or at risk for developing adolescent idiopathic scoliosis (AIS) into diagnostically or clinically useful subclasses are provided. The stratification is based on the subject's Gi? protein serine phosphorylation profile and/or the degree of imbalance in G-protein coupled receptor responses to Gi? and Gs? protein stimulation. In some embodiments, the methods involve detecting or determining the level of serine phosphorylated Gi?1 and/or Gi?3 proteins in the cell sample, and/or determining a ratio between the response to Gi? protein stimulation and the response to Gs? protein stimulation from a biological sample from the subject. Kits for predicting the risk of an AIS subject for developing a severe scoliosis, for predicting the subject's responsiveness to bracing treatment, and for identifying therapeutically useful compounds are also provided.

Abstract: The present invention provides a method of treating a subject in need thereof comprising classifying the subject into functional group FG1, FG2 or FG3, wherein i) when the subject is classified into the FG1 functional group, (A) the level of OPN or the activity of OPN in said subject is increased; (B) the subject is not treated with a brace; or (C) a combination of (A) and (B); and ii) when the subject is classified into the FG2 or FG3 functional group, (A) the level of OPN or the activity of OPN in said subject is decreased; (B) the subject is treated with a brace; or (C) a combination of (A) and (B).

Abstract: Disclosed herein are methods of determining the risk of developing a scoliosis based on the presence of at least one copy of a CD44 risk allele; methods of stratifying a subject having a scoliosis; methods of treating subjects having a scoliosis and compositions and kits for performing these methods.

Abstract: Methods of stratifying a subject having or at risk for developing adolescent idiopathic scoliosis (AIS) into diagnostically or clinically useful subclasses are provided. The stratification is based on the subject's PTP? expression and/or activity and/or PIPK1? expression and/or activity. Also provided are methods of predicting the risk of developing a scoliosis also based on the subject's PTP? expression and/or activity and/or PIPK1? expression and/or activity; and methods of increasing GiPCR signaling in cells of a subject in need thereof comprising administering to the subject's cells an effective amount of an inhibitor of PIPK1? tyrosine phosphorylation; an activator of PIPK1Y tyrosine dephosphorylation; and/or an inhibitor of PIPK1? expression and/or activity.

Abstract: There is provided a method of increasing GIPCR signalization in the cells of a subject in need thereof comprising administering to the subject an effective amount of an inhibitor of integrin alpha5beta1 expression and/or activity, whereby GiPCR signalization is increased in the cells of the subject. An inhibitor of integrin alph5beta1 may be, for example, an agent that inhibits the interaction between f osteopontin (OPN) and integrin alpha5beta1. Also provided are methods of determining the risk of developing a scoliosis and based on the presence of at least one copy of a CD44 risk allele and methods of stratifying a subject having a scoliosis and kits for performing these methods. In particular, the method of determining risk identifies SNP rs1467558; an isoleucine to threonine mutation at position 230 of CD44.

Abstract: Methods of stratifying a subject having or at risk for developing adolescent idiopathic scoliosis (AIS) into diagnostically or clinically useful subclasses are provided. The stratification is based on the subject's PTP? expression and/or activity and/or PIPK1? expression and/or activity. Also provided are methods of predicting the risk of developing a scoliosis also based on the subject's PTP? expression and/or activity and/or PIPK1? expression and/or activity; and methods of increasing GiPCR signaling in cells of a subject in need thereof comprising administering to the subject's cells an effective amount of an inhibitor of PIPK1? tyrosine phosphorylation; an activator of PIPK1Y tyrosine dephosphorylation; and/or an inhibitor of PIPK1? expression and/or activity.

Abstract: The present invention provides a method of predicting brace treatment outcome in a subject in need thereof comprising i) classifying the subject into functional group FG1, FG2 or FG3, wherein the classification enables the prediction of brace treatment outcome. Also provided are methods of determining risk of developing scoliosis, methods of treating Idiopathic scoliosis and kits for applying the methods.

Abstract: A method of classifying a subject having idiopathic scoliosis (IS) or at risk of developing IS comprising: determining the cellular response to Gi stimulation in a cell sample from the subject in the presence of OPN; determining the cellular response to Gi stimulation in a cell sample from the subject in the absence of OPN; and comparing the cellular response obtained in the presence of OPN with the cellular response obtained in the absence of OPN, whereby the comparing step enables the classification of the subject into one IS functional group. Also provided is the use of the foregoing method to classify borderline subjects and kits for applying the methods.

Abstract: Methods for diagnosing a predisposition to developing a scoliosis (e.g., adolescent idiopathic scoliosis (AIS)) and identifying compounds for treating scoliosis based on the modulation of Gi protein-coupled receptor activity are described. Specific embodiments of the methods involve measuring a change in impedance signals of cells expressing a receptor coupled to a Gi protein with a ligand. To identify compounds useful in treatment, the cell is contacted with a test compound and a ligand. A higher impedance in the presence relative to the absence of said test compound is indicative that the test compound is useful for treating scoliosis.

Abstract: Methods of stratifying a subject having or at risk for developing adolescent idiopathic scoliosis (AIS) into diagnostically or clinically useful subclasses are provided. The stratification is based on the subject's Gi? protein serine phosphorylation profile and/or the degree of imbalance in G-protein coupled receptor responses to Gi? and Gs? protein stimulation. In some embodiments, the methods involve detecting or determining the level of serine phosphorylated Gi?1 and/or Gi?3 proteins in the cell sample, and/or determining a ratio between the response to Gi? protein stimulation and the response to Gs? protein stimulation from a biological sample from the subject. Methods for predicting the risk of an AIS subject for developing a severe scoliosis, for predicting the subject's responsiveness to bracing treatment, and for identifying therapeutically useful compounds are also provided, as well as kits therefor.

Abstract: Methods for diagnosing a predisposition to developing a scoliosis (e.g., adolescent idiopathic scoliosis (AIS)) and identifying compounds for treating scoliosis based on the modulation of Gi protein-coupled receptor activity are described. Specific embodiments of the methods involve measuring a change in impedance signals of cells expressing a receptor coupled to a Gi protein with a ligand. To identify compounds useful in treatment, the cell is contacted with a test compound and a ligand. A higher impedance in the presence relative to the absence of said test compound is indicative that the test compound is useful for treating scoliosis.