title: Chondrocytes play a major role in the stimulation of bone growth by thyroid hormone.
abstract: Thyroid hormone (T3) is required for postnatal skeletal growth. It exerts its effect by binding to nuclear receptors, TRs including TRα1 and TRβ1, which are present in most cell types. These cell types include chondrocytes and osteoblasts, the interactions of which are known to regulate endochondral bone formation. In order to analyze the respective functions of T3 stimulation in chondrocytes and osteoblasts during postnatal growth, we use Cre/loxP recombination to express a dominant-negative TRα1(L400R) mutant receptor in a cell-specific manner. Phenotype analysis revealed that inhibiting T3 response in chondrocytes is sufficient to reproduce the defects observed in hypothyroid mice, not only for cartilage maturation, but also for ossification and mineralization. TRα1(L400R) in chondrocytes also results in skull deformation. In the meantime, TRα1(L400R) expression in mature osteoblasts has no visible effect. Transcriptome analysis identifies a number of changes in gene expression induced by TRα1(L400R) in cartilage. These changes suggest that T3 normally cross talks with several other signaling pathways to promote chondrocytes proliferation, differentiation, and skeletal growth.
authors.affiliation: Institut National de la Recherche Agronomique (INRA) (C.D., J.R., M.G., C.M., D.L., J.L., L.S.), UMR1313, Biologie Intégrative et Génétique Animale, Jouy-en-Josas, France; Centre National de la Recherche Scientifique (CNRS) UMR 5242 (C.C.), ENS Lyon, Institut de Génomique Fonctionnelle, Université de Lyon, Lyon, France; Institut Imagine (C.B.-L., L.L.-G.) Institut National de la Santé et de la Recherche Medicale, U1163, Université Paris Descartes, 75015 Paris, France; University of Bordeaux (O.C.), U1026, Bioingénierie Tissulaire, Bordeaux, France; and Institut de Génomique Fonctionnelle de Lyon (F.F.), Université de Lyon, CNRS, INRA, École Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Desjardin
authors.forename: Cyril
authors.initials: C
authors.lastname: Charles
authors.forename: Catherine
authors.initials: C
authors.lastname: Benoist-Lasselin
authors.forename: Julie
authors.initials: J
authors.lastname: Riviere
authors.forename: Mailys
authors.initials: M
authors.lastname: Gilles
authors.forename: Olivier
authors.initials: O
authors.lastname: Chassande
authors.forename: Caroline
authors.initials: C
authors.lastname: Morgenthaler
authors.forename: Denis
authors.initials: D
authors.lastname: Laloé
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lecardonnel
authors.forename: Frédéric
authors.initials: F
authors.lastname: Flamant
authors.forename: Laurence
authors.initials: L
authors.lastname: Legeai-Mallet
authors.forename: Laurent
authors.initials: L
authors.lastname: Schibler
mesh_terms: D000818:Animals; D001846:Bone Development; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000502:physiology*; D005260:Female; D007037:Hypothyroidism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000502:physiology*; D010012:Osteogenesis; D020239:Receptor Cross-Talk; D037021:Thyroid Hormone Receptors alpha / Q000502:physiology*; D014284:Triiodothyronine / Q000502:physiology
chemical_list: D037021:Thyroid Hormone Receptors alpha; D014284:Triiodothyronine