THYROID-HORMONE INHIBITS GROWTH AND STIMULATES TERMINAL DIFFERENTIATION OF EPIPHYSEAL GROWTH-PLATE CHONDROCYTES

As a continuation of our studies on mineralization in epiphyseal growt h plate (GP) chondrocyte cultures, the effects of tri-iodothyronine (T -3) in both beta-glycerophosphate-containing, serum-free (HL-1) and be ta-glycerophosphate-free, serum-containing medium (DATP5) were studied . The GP cells responded to T-3 in a serum-, stage-, and dosage-depend ent manner, Added at graded levels (0.1-10.0 nM) to preconflueut cultu res (from day 7) in both HL-1 and DATP5, T-3 caused progressive decrea ses in protein, collagen, and DNA synthesis but increased mineral depo sition. In postconfluent cultures, these effects of T-3 were generally muted, In preconfluent cultures, proteoglycan (PG) levels were not si gnificantly affected in DATP5, although in HL-1 they mere decreased by similar to 50%. In postconfluent cultures, T-3 increased PG levels in DATP5 but had no effect in HL-1. In HL-1, alkaline phosphatase (ALP) activity was progressively increased by 200-500% in both pre- and post confluent cultures. In DATP5 in preconfluent cultures, T-3 initially s timulated but later suppressed ALP; in postconfluent cultures, T-3 als o transiently increased ALP but did not suppress activity upon longer exposure. The inhibitory effects of T-3 on protein, PG, and DNA levels of GP chondrocytes suggest that in vivo its effects on bone growth mu st occur primarily after cellular proliferation. Apparently by binding to the 50 kDa thyroxine-binding globulin, which cannot penetrate the PG barrier, accessibility of T-3 to GP chondrocytes is limited until t he time of vascular penetration when its stimulatory effects on ALP an d mineral deposition become critical for continued bone development.