Thyroid hormone-stimulated differentiation of primary rib chondrocytes in vitro requires thyroid hormone receptor beta.
The active thyroid hormone, triiodothyronine (T(3)), binds to thyroid hormone receptors (TR) and plays an essential role in the control of chondrocyte proliferation and differentiation. Hypo- and hyperthyroidism alter the structure of growth plate cartilage and modify chondrocyte gene expression in vivo, whilst TR mutations or deletions in mice result in altered growth plate architecture. Nevertheless, the particular roles of individual TR isoforms in mediating T(3) action in chondrocytes have not been studied and are difficult to determine in vivo because of complex cellular and molecular interactions that regulate growth plate maturation. Therefore, we studied the effects of TRalpha and TRbeta on chondrocyte growth and differentiation in primary cultures of neonatal rib chondrocytes isolated from TRalpha- and TRbeta-deficient mice. T(3) decreased proliferation but accelerated differentiation of rib chondrocytes from wild-type mice. T(3) treatment resulted in similar effects in TRalpha-deficient chondrocytes, but in TRbeta-deficient chondrocytes, all T(3) responses were abrogated. Furthermore, T(3) increased TRbeta1 expression in wild-type and TRalpha-deficient chondrocytes. These data indicate that T(3)-stimulated differentiation of primary rib chondrocytes in vitro requires TRbeta and suggest that the TRbeta1 isoform mediates important T(3) actions in mouse rib chondrocytes.
Rabier
Bénédicte
B
INSERM U577-Biomatériaux et Réparation Tissulaire, Université Bordeaux 2 Victor Segalen, Zone Nord, Bâtiment 4A, 2ème étage, 33076 Bordeaux Cedex, France.
Williams
Allan J
AJ
Mallein-Gerin
Frederic
F
Williams
Graham R
GR
Chassande
O
O
D000469:Alkaline Phosphatase / Q000032:analysis; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000032:analysis; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D024121:Collagen Type X / Q000032:analysis; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012272:Ribs; D013268:Stimulation, Chemical; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000235:genetics* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*
D015415:Biomarkers; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D024121:Collagen Type X; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D016212:Transforming Growth Factor beta; D014284:Triiodothyronine; D000469:Alkaline Phosphatase