Triiodothyronine stimulation of in vitro growth and maturation of embryonic chick cartilage.

We studied the direct effect of T3 on cartilage growth and maturation in vitro. Pelvic cartilages from 9-day-old chick embryos were incubated in a serum-free organ culture system which supported cartilage growth over a 5-day interval. The addition of T3 (15 nM) to the medium increased cartilage wet weight (approximately 100%), dry weight (77%), length (35%), and total soluble protein (67%) over 3 days compared to cartilage incubated in medium alone. The DNA content was only slightly increased (2%) by T3 over the interval. T3 stimulated the same parameters of growth similarly after 5 days of incubation. In addition, T3 increased the incorporation of [14C]leucine into protein (82%) and 35SO4 into proteoglycan (53%). A dose-dependent increase in cartilage wet weight was seen with T3 (0.0015-15 nM) over 3 days of incubation. Cartilage incubated with T3 demonstrated microscopic changes in maturation, with development of large numbers of hypertrophied chondrocytes, and biochemical evidence of maturation, with increased alkaline phosphatase activity (130%). The dose-response range for T3 stimulation of alkaline phosphatase activity (0.015-0.15 nM) was considerably more restricted than that for stimulation of growth (0.0015-15 nM). These studies demonstrate that T3 in physiological concentrations directly affects cartilage growth and maturation, primarily through stimulating chondrocyte hypertrophy.