Objective—To assess the effects of supraphysiologic
concentrations of insulin-like growth factor-I (IGF-1) on
morphologic and phenotypic responses of chondrocytes.
Sample Population—Articular cartilage obtained
from 2 young horses.
Procedure—Chondrocytes were suspended in fibrin
cultures and supplemented with 25, 12.5, or 0 mg of
IGF-1/ml of fibrin. Chondrocyte morphology and phenotypic
expression were assessed histologically,
using H&E and Alcian blue stains, immunoreaction to
collagen type I and II, and in situ hybridization.
Proteoglycan content, synthesis, and monomer size
were analyzed. The DNA content was determined by
bisbenzimide-fluorometric assay, and elution of IGF-1
into medium was determined by IGF-1 radioimmunoassay.
Results—Both 12.5 and 25 µg of IGF-1/ml enhanced
phenotypic expression of chondrocytes without
inducing detrimental cellular or metabolic effects.
Highest concentration of IGF-1 (25 µg/ml) significantly
increased total DNA content, glycosaminoglycan
(GAG) content, GAG synthesis, and size of proteoglycan
monomers produced, compared with cultures
supplemented with 12.5 µg of IGF-1/ml or untreated
cultures. Histologic examination confirmed these biochemical
effects. Matrix metachromasia, type-II collagen
in situ hybridization and immunoreaction were
increased in cultures treated with 25 µg of IGF-1/ml,
compared with cultures supplemented with 12.5 µg
of IGF-1/ml or untreated cultures.
Conclusions and Clinical Relevance—Chondrocytes
exposed to high concentrations of IGF-1 maintained
differentiated chondrocyte morphology and had
enhanced synthesis of matrix molecules without
inducing apparent detrimental effects on chondrocyte
metabolism. These results suggest that application of
such composites for in vivo use during cartilage grafting
procedures should provide an anabolic effect on
the grafted cells. (Am J Vet Res 2002;63:301–305)