Metabolic and mitogenic activities of insulin-like growth factor-1 in interleukin-1-conditioned equine cartilage.
Abstract: 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. Methods: 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: 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.
Publication Date: 2000-04-20 PubMed ID: 10772110DOI: 10.2460/ajvr.2000.61.436Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research article investigates the effects of insulin-like growth factor-1 (IGF-1) on interleukin-1alpha (IL-1alpha)-conditioned equine articular cartilage. The researchers found that IGF-1 can neutralize the adverse effects of IL-1alpha, and may be useful in treating horses with osteoarthritis.
Methods and Sample Population
- The study was conducted using cartilage from the trochlea and condyles of the femur of a clinically normal 4-year-old horse.
- The cartilage explants were conditioned with interleukin-1alpha (IL-1alpha) and then treated with varying concentrations of insulin-like growth factor-1 (IGF-1).
- The researchers then evaluated the matrix responses, looking specifically at the effects on sulfated glycosaminoglycan (GAG).
- The mitogenic response was assessed by measuring the incorporation of 3H-thymidine into DNA and using a fluorometric assay of total DNA concentration.
Results
- The study found that IL-1alpha increased the amount of labeled GAG released and decreased labeled and total GAG remaining in explants. IL-1alpha also decreased mitogenic response.
- The addition of IGF-1 effectively counteracted the effects observed with IL-1alpha alone.
- Compared with IL-1alpha-treated explants, IGF-1 generally decreased total and labeled GAG release into the medium.
- Applying 500 ng/ml of IGF-1 led to a significant increase in total and newly synthesized GAG in the explants at the end of the experiment. This concentration of IGF-1 was the most effective at overcoming the adverse effects associated with IL-1alpha.
- At 200 ng/ml, IGF-1 negated the actions of IL-1alpha and restored DNA synthesis to levels similar to the negative-control explants.
Conclusions
- The results of the study suggest that IGF-1 has the potential to neutralize the detrimental effects of IL-1alpha on equine articular cartilage.
- This implies that IGF-1 treatment may be beneficial for horses suffering from osteoarthritis.
Cite This Article
APA
Frisbie DD, Sandler EA, Trotter GW, McIlwraith CW.
(2000).
Metabolic and mitogenic activities of insulin-like growth factor-1 in interleukin-1-conditioned equine cartilage.
Am J Vet Res, 61(4), 436-441.
https://doi.org/10.2460/ajvr.2000.61.436 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523, USA.
MeSH Terms
- Animals
- Cartilage / drug effects
- Cartilage / metabolism
- Culture Media
- Culture Techniques
- DNA Replication / drug effects
- Glycosaminoglycans / metabolism
- Horses / metabolism
- Humans
- Insulin-Like Growth Factor I / metabolism
- Interleukin-1 / pharmacology
- Mitosis / drug effects
- Recombinant Proteins / pharmacology
Citations
This article has been cited 1 times.- Tung JT, Fenton JI, Arnold C, Alexander L, Yuzbasiyan-Gurkan V, Venta PJ, Peters TL, Orth MW, Richardson DW, Caron JP. Recombinant equine interleukin-1beta induces putative mediators of articular cartilage degradation in equine chondrocytes. Can J Vet Res 2002 Jan;66(1):19-25.
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