Characterization of thyroid hormone (T3) receptors in three osteosarcoma cell lines of distinct osteoblast phenotype: interactions among T3, vitamin D3, and retinoid signaling.
T3 is required for normal skeletal development, but its cellular targets in bone are unknown. T3 regulates target gene transcription via a specific nuclear receptor (T3R), which can heterodimerize with 9-cis-retinoic acid, 1 alpha, 25-dihydroxyvitamin D3, or retinoic acid receptors to modify T3 responsiveness. Serum-free cultures were developed to investigate hormone interactions in three osteosarcoma cell lines, ROS25/1, UMR106, and ROS17/2.8, that express fibroblast-like, preosteoblast, and mature osteoblast phenotypes. ROS25/1 expressed T3R alpha 1, but only low levels of T3R beta 1, whereas UMR106 and ROS17/2.8 cells expressed both receptor proteins. All cells expressed c-erb-A alpha 2 protein and equal levels of 1 alpha,25-dihydroxyvitamin D3 receptor, 9-cis-retinoic acid receptor, and retinoic acid receptor messenger RNAs. Endogenous T3R activity and the effects of D3 and 9-cis-RA on T3 responsiveness were determined in transfections using reporter genes containing T3 response elements from rat malic enzyme or alpha-myosin heavy chain genes. Cell-specific T3 responses were associated with differing patterns of T3R gene expression and stages of osteoblast phenotype expression. A change in T3R beta 1 gene expression during osteoblast phenotype differentiation may modify T3 action in developing bone.
Williams
G R
GR
Department of Medicine, University of Birmingham, Edgbaston, United Kingdom.
Bland
R
R
Sheppard
M C
MC
D000818:Animals; D001483:Base Sequence; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002762:Cholecalciferol / Q000494:pharmacology; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000378:metabolism* / Q000502:physiology; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012176:Retinoids / Q000494:pharmacology; D015398:Signal Transduction; D014284:Triiodothyronine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015335:Molecular Probes; D011988:Receptors, Thyroid Hormone; D012176:Retinoids; D014284:Triiodothyronine; D002762:Cholecalciferol