Biomarkers of osteoarthritis

a biomarker and osteoarthritis technology, applied in the field of disease biomarkers, can solve the problems of osteoarthritis risk or suspected osteoarthritis of subjects

Inactive Publication Date: 2011-09-08
UNIVERSITY OF MISSOURI
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Benefits of technology

[0010]In another aspect, the present disclosure provides a method for monitoring the effect of a treatment of osteoarthritis in a subject comprising: a) obtaining a first OA biomarker expression profile comprising measuring the expression level of two or more OA polypeptides selected from the group consisting of MCP1, IL8, KC, MMP2, MMP3, IL6, MMP1, RANTES, MMP9, IL1B, Apolipoprotein A1, Apolipoprotein E, DCN, CILP and COMP in a first biological sample obtained from the subject before the osteoarthritis treatment is administered to the subject; b) obtaining a second OA biomarker expression profile comprising measuring the expression level

Problems solved by technology

In the method, the subject can be at risk of h

Method used

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Examples

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example 1

Assessment of Proteins in Media from In Vitro Cultured Normal and OA Articular Cartilage Explants

[0087]Articular cartilage was harvested from the femoral head of dogs (n=6) undergoing total hip replacement due to chronic OA and from dogs (n=6) with no overt clinical signs of OA and euthanized for reasons unrelated to the present study. Two 4mm explants were created from the tissue of each animal and incubated in 500 μl of DMEM with supplemental nutrients for 7 days. Culture media from each individual was analyzed using a canine cytokine and chemokine immunoassay for MCP1, IL-8 and KC (Millipore) based on the xMAP platform. A second aliquot was analyzed using a multiplex human MMP immunoassay for MMPs 2, 3 and 13 (R&D Systems) that has been shown to cross react with canine samples. Clinically relevant subgroups were then created based on OA-status and the media from each subgroup was pooled for proteomics analysis. Each media pool was acetone precipitated and quantified to ensure equ...

example 2

Assessment of Synovial Fluid and Serum Cytokines, Chemokines and Matrix Metalloproteinases (MMPs) in Dogs with Spontaneously Occurring OA

[0094]Methods: Informed client consent was obtained for each dog included in this study. Blood and synovial fluid were obtained from 10 adult medium and large breed dogs presenting to the UMC-VMTH for surgical intervention of unilateral stifle (knee) OA (Pre-Op OA; n=10). These dogs ranged from 3-8 years old (mean 5.15 years median might be better). Synovial fluid was obtained from the affected stifle via routine aseptic arthrocentesis, and blood was collected via jugular venipuncture. Clinical knee OA was confirmed in each dog by a board-certified veterinary orthopaedic surgeon. Radiographic evidence of OA was confirmed by a board-certified veterinary radiologist. All dogs underwent knee surgery for cruciate ligament deficiency and recovered uneventfully. Eight to 12 weeks later, the dogs returned for a post-operative re-check, and blood and synov...

example 3

OA Biomarkers in Synovial Fluid of Human Patients

[0101]OA biomarkers in the synovial fluid of human patients were investigated. Specific goals were 1) to identify and measure the concentration of specific MMPs and inflammatory cytokines released to the synovial fluid of normal and OA patients undergoing total knee arthroplasty; and 2) to correlate the production of these inflammatory biomarkers with radiographic severity of disease. All procedures were performed with IRB (IRB#1042248) approval. Synovial fluid was aspirated from three “true normal” patients (23, 27, 28 y / o) with no previous knee injury, clinical symptoms of knee pain or OA, or operative procedures performed. Synovial fluid was aspirated from 18 patients (21 knees) with OA immediately preceding their total knee arthroplasty procedure (age range=44-86 y / o). Equal volumes of hyaluronidase treated synovial fluid samples were analyzed using the Fluorokine MAP human MMP (MMP-1, -2,-9, and 013) and cytokine (Interleukin 1β ...

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Abstract

Biomarkers, biomarker panels and methods for diagnosing osteoarthritis (OA) are disclosed, using measurement of the expression level of certain polypeptides in a test sample from a subject, including MCP1, IL8, KC, MMP2, MMP3, IL6, MMP1, RANTES, MMP9, IL1B, Apolipoprotein A1, Apolipoprotein E, DCN, CILP and COMP. Related methods for monitoring OA treatment efficacy, diagnostic reagents, and kits are also described.

Description

REFERENCE TO RELATED APPLICATIONS [0001]This application claims the benefit of U.S. provisional application 61 / 339,511, filed Mar. 5, 2010, the entire contents of which is hereby incorporated by reference.FIELD OF THE INVENTION [0002]The present disclosure relates to biomarkers of disease and more particularly to a plurality of biomarkers, related methods and kits for diagnosing, staging, and monitoring osteoarthritis.BACKGROUND [0003]Osteoarthritis (OA) is a debilitating disease that affects human and veterinary, particularly canine patients. Because OA is not typically diagnosed early enough to prevent the clinical progression of disease, development of early OA biomarkers has profound ramifications for diagnostic screening, disease staging, treatment planning and monitoring.[0004]In dogs, certain proteins exhibit differential expression levels in synovial fluid when OA is experimentally induced. These are monocyte chemoattractant protein 1 (MCP1), interleukin 8 (IL8) and keratino...

Claims

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Application Information

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IPC IPC(8): C40B30/04C12Q1/68G01N33/53G01N33/566G01N33/00C40B40/10G01N27/447G01N33/559H01J49/26
CPCC12Q1/6883C12Q2600/112G01N33/5308G01N2800/105G01N2800/56C12Q2600/136G01N33/6887G01N2333/52G01N2333/5421
Inventor COOK, JAMES L.COOK, CRISTI R.STOKER, AARON M.KUROKI, KEIICHIGARNER, BRIDGET COLLEENEVANS, RICHARDROLLER, BRANDON LEEJAYABALAN, PRAKASH SIDHA
Owner UNIVERSITY OF MISSOURI
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