Insulin-like growth factor 1 and corticosteroid modulation of chondrocyte metabolic and mitogenic activities in interleukin 1-conditioned equine cartilage.
OBJECTIVE
To evaluate potential stimulatory or matrix-sparing effects of insulin-like growth factor 1 (IGF-1), alone or in combination with a corticosteroid, in an interleukin 1 (IL-1)-induced model of cartilage degradation.


METHODS
Cartilage from the weightbearing surfaces of trochlea and condyles of clinically normal 2-year-old male horses.


METHODS
Triamcinolone acetonide and IGF-1 effects were evaluated by assessing: matrix responses by sulfated glycosaminoglycan (GAG) assay and [35S]sulfated GAG synthesis; collagen content by hydroxyproline assay; and mitogenic response by [3H]thymidine incorporation into DNA and fluorometric assay of total DNA concentration.


RESULTS
Conditioning of cartilage explants with 10 ng of human recombinant IL-1 alpha increased degradation and decreased synthesis of matrix proteoglycans (PG), without affecting matrix collagen content. Human recombinant IGF-1 decreased PG loss and reversed the reduction of PG synthesis in cartilage explants conditioned with IL-1. Given alone, steroids decreased PG concentration and synthetic rate in normal cartilage. However, the previously diminished PG content, attributable to IL-1 conditioning, was not further exacerbated by steroid administration in IL-1-conditioned explants. Combined treatment of normal cartilage explants with IGF-1 and steroids resulted in PG preservation and increase in collagen content. Similar PG and collagen effects were not evident when treating IL-1-conditioned cartilage with IGF-1/steroid combinations. Decrease in chondrocyte proliferation was associated with steroid administration. Exposure to IGF and steroids prevented the decrease in mitogenesis that could lead to cellular loss, particularly in IL-1-conditioned explants.


CONCLUSIONS
Combination IGF-1 and steroid treatment of normal cartilage cultures indicated substantial ability to override the anabolic suppression associated with steroids alone. Potentially, administration of corticosteroids, followed by IGF-1, may act to decrease propagation of detrimental mediator release while allowing appreciation of the chondroenhancing effects of IGF-1. These beneficial effects were considerably reduced in IL-1-induced cartilage damage.
Frisbie
D D
DD
Comparative Orthopaedics Laboratory, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Nixon
A J
AJ
D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002356:Cartilage / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis / Q000378:metabolism; D004247:DNA / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D004347:Drug Interactions; D006025:Glycosaminoglycans / Q000032:analysis / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology; D006734:Horse Diseases / Q000139:chemically induced / Q000378:metabolism; D006736:Horses / Q000378:metabolism* / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000009:adverse effects / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D010003:Osteoarthritis / Q000139:chemically induced / Q000378:metabolism / Q000662:veterinary; D011509:Proteoglycans / Q000032:analysis / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D013462:Sulfur Radioisotopes; D013936:Thymidine / Q000032:analysis / Q000378:metabolism; D014222:Triamcinolone Acetonide / Q000494:pharmacology; D014316:Tritium
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D006025:Glycosaminoglycans; D007375:Interleukin-1; D011509:Proteoglycans; D013431:Sulfates; D013462:Sulfur Radioisotopes; D014316:Tritium; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D004247:DNA; D014222:Triamcinolone Acetonide; D013936:Thymidine