Insulin-like growth factor 1 and corticosteroid modulation of chondrocyte metabolic and mitogenic activities in interleukin 1-conditioned equine cartilage.

The research article evaluates the effects of insulin-like growth factor 1 (IGF-1) and a corticosteroid in mitigating cartilage degradation caused by interleukin 1 (IL-1). They found that combining IGF-1 and corticosteroids can counteract the damaging effects caused by IL-1 in normal cartilage, but these benefits were diminished in already damaged cartilage.

Experiment Design

• This study was conducted using cartilage from healthy two-year-old male horses. Specifically, the weightbearing surfaces of the trochlea and condyles were examined.
• The researchers then evaluated the effects of Triamcinolone acetonide, a corticosteroid, and IGF-1. They did so by assessing matrix responses using a sulfated glycosaminoglycan (GAG) assay and a radioisotope-labelled [35S]sulfated GAG synthesis.
• Collagen content was determined by a hydroxyproline assay, and mitogenic response was measured by [3H]thymidine incorporation into DNA and a fluorometric assay of total DNA concentration.

Results Found

• The study found that conditioning cartilage explants with 10 ng of human recombinant IL-1 alpha increased degradation and reduced the synthesis of matrix proteoglycans (PG), without affecting matrix collagen content.
• Human recombinant IGF-1 decreased the loss of PG and reversed the reduction of PG synthesis in cartilage explants conditioned with IL-1.
• When given alone, steroids were found to decrease PG concentration and synthetic rate in normal cartilage. Despite this, the previously diminished PG content, attributable to IL-1 conditioning, was not further exacerbated by steroid administration.
• Combining treatments of IGF-1 and steroids resulted in an increase in collagen content and preservation of PG in normal cartilage explants. Similar effects were not observed in IL-1 conditioned cartilage when treated with the same combination.
• Steroid administration was associated with a decrease in chondrocyte proliferation, but exposing these cells to IGF and steroids prevented the decrease in mitogenesis that could lead to cellular loss.

Conclusions and Implications

• The research concluded that combining IGF-1 and steroid treatment showed promising results in overcoming the anabolic suppression associated with individual steroid treatment.
• Administering corticosteroids, followed by IGF-1, may act to decrease the propagation of harmful mediator release while promoting the chondroenhancing effects of IGF-1.
• However, these beneficial effects were considerably reduced in IL-1-induced cartilage damage, suggesting a potentially greater benefit in earlier intervention or prevention scenarios.