Endocrinology, Vol 135, 2375-2385, Copyright © 1994 by Endocrine Society

ARTICLES

Characterization of thyroid hormone (T3) receptors in three osteosarcoma cell lines of distinct osteoblast phenotype: interactions among T3, vitamin D3, and retinoid signaling

GR Williams, R Bland and MC Sheppard
Department of Medicine, University of Birmingham, Edgbaston, United Kingdom.

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.

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