Diagnosis and treatment of skeletal degeneration conditions
OwnerKaren E. Yates, Shuichi Mizuno +1inventors
InventorsKaren E. Yates, Shuichi Mizuno, Julie Glowacki
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Abstract
This invention relates to methods and compositions for the diagnosis and treatment of conditions that affect skeletal growth. More specifically, the invention relates to isolated molecules that can be used to promote chondrogenesis. These molecules, therefore, are useful in the treatment of various disorders that affect the skeleton, including bone and cartilage degeneration conditions.
Claims61
An isolated nucleic acid molecule selected from the group consisting of:
- (a) a nucleic acid molecule which hybridizes under stringent conditions to a molecule consisting of a nucleotide sequence set forth as any of SEQ ID NO:1-11, and which codes for a polypeptide that induces differentiation of a mesenchymal cell,
- (b) nucleic acid molecules that differ from the nucleic acid molecules of (a) in codon sequence due to the degeneracy of the genetic code, and
- (c) complements of (a) or (b).
An isolated nucleic acid molecule selected from the group consisting of
- (a) unique fragments of a nucleotide sequence set forth as any of SEQ ID NO:1-11, and
- (b) complements of (a),
- provided that a unique fragment of (a) includes a sequence of contiguous nucleotides which is not identical to any sequence in the prior art and any complements or fragments thereof.
A method for determining the level of any of SEQ ID NO:1-11 expression in a subject, comprising measuring expression of any of SEQ ID NO:1-11 in a test sample from the subject to determine the level of any of SEQ ID NO:1-11 expression in the subject.
A method for identifying an agent useful in modulating mesenchymal cell differentiation induction activity of a molecule, comprising:
- (a) contacting a molecule having mesenchymal cell differentiation induction activity with a candidate agent,
- (b) measuring mesenchymal cell differentiation induction activity of the molecule, and
- (c) comparing the measured mesenchymal cell differentiation induction activity of the molecule to a control to determine whether the candidate agent modulates mesenchymal cell differentiation induction activity of the molecule,
- wherein the molecule is a nucleic acid molecule selected from the group consisting of SEQ ID NO:1-11, and 13-66, or an expression product thereof.
A method of diagnosing a condition characterized by aberrant expression of a nucleic acid molecule or an expression product thereof, said method comprising:
- a) contacting a biological sample from a subject with an agent, wherein said agent specifically binds to said nucleic acid molecule, an expression product thereof, or a fragment of an expression product thereof;
- and
- b) measuring the amount of bound agent and determining therefrom if the expression of said nucleic acid molecule or of an expression product thereof is aberrant, aberrant expression being diagnostic of the condition;
- wherein the nucleic acid molecule is at least one nucleic acid molecule selected from the group consisting of SEQ ID NO:1-11, and 13-66.
A method for determining regression, progression or onset of a cartilaginous tissue degeneration condition in a subject characterized by aberrant expression of a nucleic acid molecule or an expression product thereof, comprising:
- monitoring a sample from a patient, for a parameter selected from the group consisting of
- (i) a nucleic acid molecule selected from the group consisting of SEQ ID NO:1-11, and 13-66,
- (ii) a polypeptide encoded by the nucleic acid,
- (iii) a peptide derived from the polypeptide, and
- (iv) an antibody which selectively binds the polypeptide or peptide,
- as a determination of regression, progression or onset of said cartilaginous tissue degeneration condition in the subject.
A method for treating a cartilaginous tissue degeneration condition, comprising:
- administering to a subject in need of such treatment an agent that modulates expression of a molecule selected from the group consisting of SEQ ID NO:1-67, in an amount effective to treat the cartilaginous tissue degeneration condition.
A method for treating a subject to reduce the risk of a cartilaginous tissue degeneration condition developing in the subject, comprising:
- administering to a subject who is known to express decreased levels of a molecule selected from the group consisting of SEQ ID NO:1-67, an agent for reducing the risk of cartilaginous tissue degeneration condition in an amount effective to lower the risk of the subject developing a future cartilaginous tissue degeneration condition,
- wherein the agent is selected from the group consisting of an osteogenic protein, Insulin-like Growth Factor, Transforming Growth Factor-β, and a proteoglycan, or an agent that modulates expression of a molecule selected from the group consisting of consisting of SEQ ID NO:1-67.
A method for identifying a candidate agent useful in the treatment of a cartilaginous tissue degeneration condition, comprising:
- determining expression of a set of nucleic acid molecules in a cell of mesenchymal origin or cartilaginous tissue under conditions which, in the absence of a candidate agent, permit a first amount of expression of the set of nucleic acid molecules, wherein the set of nucleic acid molecules comprises at least one nucleic acid molecule selected from the group consisting of SEQ ID NO:1-11, and 13-66,
- contacting the cell of mesenchymal origin or cartilaginous tissue with the candidate agent, and
- detecting a test amount of expression of the set of nucleic acid molecules, wherein an increase in the test amount of expression in the presence of the candidate agent relative to the first amount of expression indicates that the candidate agent is useful in the treatment of the cartilaginous tissue degeneration condition.
A pharmaceutical composition, comprising:
- an agent comprising an isolated nucleic acid molecule selected from the group consisting of SEQ ID NO:1-11, and 13-66, or an expression product thereof, in a pharmaceutically effective amount to treat a cartilaginous tissue degeneration condition, and
- a pharmaceutically acceptable carrier.
A solid-phase nucleic acid molecule array consisting essentially of a set of nucleic acid molecules, expression products thereof, or fragments thereof, each nucleic acid molecule selected from the group consisting of SEQ ID NO:1-11, and 13-66, fixed to a solid substrate.
Dependencies are inferred from the claim text.