Thyroid hormone inhibits growth and stimulates terminal differentiation of epiphyseal growth plate chondrocytes.
As a continuation of our studies on mineralization in epiphyseal growth plate (GP) chondrocyte cultures, the effects of tri-iodothyronine (T3) in both beta-glycerophosphate-containing, serum-free (HL-1) and beta-glycerophosphate-free, serum-containing medium (DATP5) were studied. The GP cells responded to T3 in a serum-, stage-, and dosage-dependent manner. Added at graded levels (0.1-10.0 nM) to preconfluent cultures (from day 7) in both HL-1 and DATP5, T3 caused progressive decreases in protein, collagen, and DNA synthesis but increased mineral deposition. In postconfluent cultures, these effects of T3 were generally muted. In preconfluent cultures, proteoglycan (PG) levels were not significantly affected in DATP5, although in HL-1 they were decreased by approximately 50%. In postconfluent cultures, T3 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 postconfluent cultures. In DATP5 in preconfluent cultures, T3 initially stimulated but later suppressed ALP; in postconfluent cultures, T3 also transiently increased ALP but did not suppress activity upon longer exposure. The inhibitory effects of T3 on protein, PG, and DNA levels of GP chondrocytes suggest that in vivo its effects on bone growth must occur primarily after cellular proliferation. Apparently by binding to the 50 kDa thyroxine-binding globulin, which cannot penetrate the PG barrier, accessibility of T3 to GP chondrocytes is limited until the time of vascular penetration when its stimulatory effects on ALP and mineral deposition become critical for continued bone development.
Ishikawa
Y
Y
Department of Chemistry and Biochemistry, and School of Medicine, University of South Carolina, Columbia 29208, USA.
Genge
B R
BR
Wuthier
R E
RE
Wu
L N
LN
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D019902:Chondrocytes / Q000187:drug effects* / Q000201:enzymology; D003094:Collagen / Q000096:biosynthesis; D006132:Growth Plate / Q000187:drug effects* / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis; D013975:Thyroxine-Binding Proteins / Q000378:metabolism; D013977:Tibia; D014284:Triiodothyronine / Q000494:pharmacology*
D011509:Proteoglycans; D013975:Thyroxine-Binding Proteins; D014284:Triiodothyronine; D003094:Collagen; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase