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

Abstract

OBJECTIVE: To determine response of interleukin-1alpha (IL-1alpha)-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-1alpha 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-1alpha (40 ng/ml) increased the amount of labeled GAG released and decreased labeled and total GAG remaining in explants, and IL-1alpha decreased mitogenic response. Addition of IGF-1 counteracted effects seen with IL-1alpha alone. In general, IGF-1 decreased total and labeled GAG released into the medium, compared with IL-1alpha-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-1alpha alone. Concentrations of 200 ng of IGF-1/ml abolished actions of IL-1alpha 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-1alpha in in vitro explants. These beneficial effects may be useful in horses with osteoarthritis.