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

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

Search for other papers by David D. Frisbie in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Emily A. Sandler Equine Orthopedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

Search for other papers by Emily A. Sandler in
Current site
Google Scholar
PubMed
Close
,
Gayle W. Trotter Equine Orthopedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

Search for other papers by Gayle W. Trotter in
Current site
Google Scholar
PubMed
Close
 DVM, MS
, and
C. Wayne McIlwraith Equine Orthopedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

Search for other papers by C. Wayne McIlwraith in
Current site
Google Scholar
PubMed
Close
 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)

All Time Past Year Past 30 Days
Abstract Views 22 0 0
Full Text Views 5385 5235 1652
PDF Downloads 71 42 2
Advertisement