Insulin and thyroid hormones stimulate matrix metabolism in primary cultures of articular chondrocytes from young rabbits independently and in combination

These studies examined the effects of heat-inactivated horse serum, insulin, triiodothyronine (T3), and thyroxine (T4), individually and in combination, on collagen and proteoglycan synthesis by primary cell cultures of articular chondrocytes from immature male rabbits. Insulin concentrations of 25 to 100 ng/ml (4.4 to 17.4 x 10(-9) M) increasingly stimulated collagen and proteoglycan synthesis in the absence of serum. The effects of 25 ng/ml (4.4 x 10(-9) M) insulin or 15% heat-inactivated horse serum on collagen synthesis were similar. Triiodothyronine (10(-10) to 10(-6) M) and T4 (10(-8) to 10(-4) M) also stimulated collagen synthesis in the absence of serum, with peak effects at 10(-8) and 10(-6) M, respectively. Biphasic stimulation of proteoglycan synthesis was obtained with 10(-11) to 10(-7) MT3 (maximum at 10(-8) M) and 10(-8) to 10(-5) M T4 (maximum at 10(-7) M). In these experiments, triiodothyronine was 10 to 100 times more potent than T4 in stimulating cartilage matrix production. The cells retained their chondrocytic phenotype under hormonal stimulation, secreting almost exclusively Type II collagen and large, chondroitin sulfate-rich proteoglycans. The addition of insulin to maximally-stimulating concentrations of either T3 or T4 in serum-free medium further stimulated matrix synthesis, suggesting that these hormones modulate chondrocyte metabolism via multiple biosynthetic/receptor pathways.