Prevention and treatment of osteoarthritis
AssigneeUniversity of Kansas
InventorJinxi Wang
Life of this patent
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Abstract
Subjects lacking Nfat1 display osteoarthritis in weight-bearing joints. Osteoarthritic changes associated with Nfat1 deficiency are characterized by articular cartilage degradation, articular chondrocyte proliferation/clustering, progressive articular surface destruction, periarticular chondro-osteophyte formation, and exposure of thickened subchondral bone. Methods of treating osteoarthritis, methods of diagnosis and early prediction of the onset of osteoarthritis, and methods for screening drug candidates that may be useful for treatment of osteoarthritis are presented.
Claims12
A method of diagnosing primary osteoarthritis and/or predicting susceptibility to primary osteoarthritis in a subject, comprising:
- measuring the subject's Nfat1 protein or gene expression level or an Nfat1 transcription factor activity in a tissue sample selected from cartilage or peripheral blood cells;
- diagnosing primary osteoarthritis and/or predicting susceptibility to primary osteoarthritis in the subject based on the measuring, wherein the diagnosing includes comparing the subject's Nfat1 protein or gene expression level or the Nfat1 transcription factor activity to a wild-type control Nfat1 protein or gene expression level or an Nfat1 transcription factor activity, wherein having Nfat1 protein or gene expression levels or Nfat1 transcription factor activity reduced by at least 50% relative to the wild-type control is predictive of susceptibility to osteoarthritis;
- administering at least one bioactive substance selected from the group consisting of an Nfat1 protein and a nucleic acid encoding an Nfat1 protein to the subject;
- and
- determining whether the bioactive substance increases at least one of Nfat1 protein expression, Nfat1 gene expression, or Nfat1 transcription factor activity in cartilage or peripheral blood cells in the subject.
A method of diagnosing primary osteoarthritis and/or predicting susceptibility to primary osteoarthritis in a subject, comprising:
- measuring a subject's Nfat1 protein or gene expression level or an Nfat1 transcription factor activity in a tissue sample selected from cartilage or peripheral blood cells;
- and
- diagnosing primary osteoarthritis and/or predicting susceptibility to primary osteoarthritis in the subject based on the measuring, wherein having Nfat1 protein or gene expression levels or Nfat1 transcription factor activity reduced by at least 50% relative to the wild-type control is predictive of susceptibility to osteoarthritis;
- and
- administering an agent to the subject to increase Nfat1 protein or gene expression or to increase Nfat1 transcription factor activity in cartilage tissue in the subject, wherein the agent is selected from the group consisting of an Nfat1 protein, a nucleic acid encoding an Nfat1 protein, and combinations thereof.
Dependencies are inferred from the claim text.