INSULIN AND THYROID-HORMONES STIMULATE MATRIX METABOLISM IN PRIMARY CULTURES OF ARTICULAR CHONDROCYTES FROM YOUNG-RABBITS INDEPENDENTLY ANDIN COMBINATION

These studies examined the effects of heat-inactivated horse serum, in sulin, triiodothyronine (T-3), and thyroxine (T-4), individually and i n combination, on collagen and proteoglycan synthesis by primary cell cultures of articular chondrocytes from immature mate rabbits. Insulin concentrations of 25 to 100 ng/ml (4.4 to 17.4 x 10(-9) M) increasing ly stimulated collagen and proteoglycan synthesis in the absence of se rum. The effects of 25 ng/ml (4.4 x 10(-9) M) insulin or 15% heat-inac tivated horse serum on collagen synthesis were similar. Triiodothyroni ne (10(-10) to 10(-6) M) and T-4 (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 synt hesis was obtained with 10(-11) to 10(-7) MT(3), (maximum at 10(-8) M) and 10(-8) to 10(-5) MT(4) (maximum at 10(-7) M). In these experiment s, triiodothyronine was 10 to 100 times more potent than T-4 in stimul ating cartilage matrix production. The cells retained their chondrocyt ic phenotype under hormonal stimulation, secreting almost exclusively Type II collagen and large, chondroitin sulfate-rich proteoglycans. Th e addition of insulin to maximally-stimulating concentrations of eithe r T-3 or T-4 in serum-free medium further stimulated matrix synthesis, suggesting that these hormones modulate chondrocyte metabolism via mu ltiple biosynthetic/receptor pathways.