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Metabolic and mitogenic activities of insulin-like growth factor-1 in interleukin-1-conditioned equine cartilage

David D. FrisbieEquine Orthopedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Emily A. SandlerEquine Orthopedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Gayle W. TrotterEquine Orthopedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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C. Wayne McIlwraithEquine Orthopedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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 BVSc, PhD

Abstract

Objective—To determine response of interleukin-1α (IL-1α)-conditioned equine articular cartilage explants to insulin-like growth factor-1 (IGF-1).

Sample Population—Cartilage from the trochlea and condyles of the femur of a clinically normal 4-year-old horse.

Procedure—Effects of IGF-1 (0 to 500 ng/ml) after addition of IL-1α were evaluated by assessing matrix responses, using a sulfated glycosaminoglycan (GAG) assay, matrix 35SO4 GAG incorporation, and release of GAG. Mitogenic response was assessed by 3H-thymidine incorporation into DNA and fluorometric assay of total DNA concentration.

Results—Human recombinant IL-1α (40 ng/ml) increased the amount of labeled GAG released and decreased labeled and total GAG remaining in explants, and IL-1α decreased mitogenic response. Addition of IGF-1 counteracted effects seen with IL-1α alone. In general, IGF-1 decreased total and labeled GAG released into the medium, compared with IL-1α- treated explants (positive-control sample). Values for these variables did not differ significantly from those for negative-control explants. A significant increase in total and newly synthesized GAG in the explants at termination of the experiment was observed with 500 ng of IGF-1/ml. Labeled GAG remaining in explants was greater with treatment at 50 ng of IGF-1/ml, compared with treatment with IL-1α alone. Concentrations of 200 ng of IGF-1/ml abolished actions of IL-1α and restored DNA synthesis to values similar to those of negative-control explants.

Conclusions and Clinical Relevance—IGF-1 at 500 ng/ml was best at overcoming detrimental effects associated with IL-1α in in vitro explants. These beneficial effects may be useful in horses with osteoarthritis. (Am J Vet Res 2000;61:436–441)

Abstract

Objective—To determine response of interleukin-1α (IL-1α)-conditioned equine articular cartilage explants to insulin-like growth factor-1 (IGF-1).

Sample Population—Cartilage from the trochlea and condyles of the femur of a clinically normal 4-year-old horse.

Procedure—Effects of IGF-1 (0 to 500 ng/ml) after addition of IL-1α were evaluated by assessing matrix responses, using a sulfated glycosaminoglycan (GAG) assay, matrix 35SO4 GAG incorporation, and release of GAG. Mitogenic response was assessed by 3H-thymidine incorporation into DNA and fluorometric assay of total DNA concentration.

Results—Human recombinant IL-1α (40 ng/ml) increased the amount of labeled GAG released and decreased labeled and total GAG remaining in explants, and IL-1α decreased mitogenic response. Addition of IGF-1 counteracted effects seen with IL-1α alone. In general, IGF-1 decreased total and labeled GAG released into the medium, compared with IL-1α- treated explants (positive-control sample). Values for these variables did not differ significantly from those for negative-control explants. A significant increase in total and newly synthesized GAG in the explants at termination of the experiment was observed with 500 ng of IGF-1/ml. Labeled GAG remaining in explants was greater with treatment at 50 ng of IGF-1/ml, compared with treatment with IL-1α alone. Concentrations of 200 ng of IGF-1/ml abolished actions of IL-1α and restored DNA synthesis to values similar to those of negative-control explants.

Conclusions and Clinical Relevance—IGF-1 at 500 ng/ml was best at overcoming detrimental effects associated with IL-1α in in vitro explants. These beneficial effects may be useful in horses with osteoarthritis. (Am J Vet Res 2000;61:436–441)