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Gene biomarkers in peripheral white blood cells of horses with experimentally induced osteoarthritis

J. Lacy KammGail Holmes Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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David D. FrisbieGail Holmes Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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C. Wayne McIlwraithGail Holmes Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Kindra E. OrrRood and Riddle Equine Hospital, 2150 Georgetown Rd, Lexington, KY 40511.

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Abstract

Objective—To use microarray analysis to identify genes that are differentially expressed in horses with experimentally induced osteoarthritis.

Animals—24 horses.

Procedures—During arthroscopic surgery, a fragment was created in the distal aspect of the radiocarpal bone in 1 forelimb of each horse to induce osteoarthritis. At day 14 after osteoarthritis induction, horses began exercise on a treadmill. Blood and synovial fluid samples were collected before and after surgery. At day 70, horses were euthanized and tissues were harvested for RNA analysis. An equine-specific microarray was used to measure RNA expression in peripheral WBCs. These data were compared with mRNA expression (determined via PCR assay) in WBCs, cartilage, and synovium as well as 2 protein biomarkers of cartilage matrix turnover in serum and synovial fluid.

Results—A metalloproteinase domain-like protein decysin-1 (ADAMDEC1), glucose-regulated protein (GRP) 94, hematopoietic cell signal transducer (HCST), Unc-93 homolog A (hUNC-93A), and ribonucleotide reductase M2 polypeptide (RRM2) were significantly differentially regulated in WBCs of horses with osteoarthritis, compared with values prior to induction of osteoarthritis. There was correlation between the gene expression profile in WBCs, cartilage, and synovium and the cartilage turnover proteins. Gene expression of ADAMDEC1, hUNC-93A, and RRM2 in WBCs were correlated when measured via microarray analysis and PCR assay.

Conclusions and Clinical Relevance—Expression of ADAMDEC1, GRP94, HCST, hUNC-93A, and RRM2 was differentially regulated in peripheral WBCs obtained from horses with experimentally induced osteoarthritis. Gene expression of ADAMDEC1, hUNC-93A, and RRM2 in peripheral WBCs has the potential for use as a diagnostic aid for osteoarthritis in horses.

Abstract

Objective—To use microarray analysis to identify genes that are differentially expressed in horses with experimentally induced osteoarthritis.

Animals—24 horses.

Procedures—During arthroscopic surgery, a fragment was created in the distal aspect of the radiocarpal bone in 1 forelimb of each horse to induce osteoarthritis. At day 14 after osteoarthritis induction, horses began exercise on a treadmill. Blood and synovial fluid samples were collected before and after surgery. At day 70, horses were euthanized and tissues were harvested for RNA analysis. An equine-specific microarray was used to measure RNA expression in peripheral WBCs. These data were compared with mRNA expression (determined via PCR assay) in WBCs, cartilage, and synovium as well as 2 protein biomarkers of cartilage matrix turnover in serum and synovial fluid.

Results—A metalloproteinase domain-like protein decysin-1 (ADAMDEC1), glucose-regulated protein (GRP) 94, hematopoietic cell signal transducer (HCST), Unc-93 homolog A (hUNC-93A), and ribonucleotide reductase M2 polypeptide (RRM2) were significantly differentially regulated in WBCs of horses with osteoarthritis, compared with values prior to induction of osteoarthritis. There was correlation between the gene expression profile in WBCs, cartilage, and synovium and the cartilage turnover proteins. Gene expression of ADAMDEC1, hUNC-93A, and RRM2 in WBCs were correlated when measured via microarray analysis and PCR assay.

Conclusions and Clinical Relevance—Expression of ADAMDEC1, GRP94, HCST, hUNC-93A, and RRM2 was differentially regulated in peripheral WBCs obtained from horses with experimentally induced osteoarthritis. Gene expression of ADAMDEC1, hUNC-93A, and RRM2 in peripheral WBCs has the potential for use as a diagnostic aid for osteoarthritis in horses.

Contributor Notes

Address correspondence to Dr. Frisbie (david.frisbie@colostate.edu).