Expression of multiple thyroid hormone receptor isoforms in rat femoral and vertebral bone and in bone marrow osteogenic cultures

Thyroid hormones influence both bone formation and bone resorption. Clinical data and animal studies provide evidence of skeletal site heterogeneity (hip vs. spine) of bone responses to thyroid hormones. In vitro studies also demonstrate direct effects of thyroid hormones on cells of the osteoblast lineage. Transcriptional regulation by thyroid hormone is mediated by ligand‐dependent transcription factors called thyroid hormone receptors (TRs). Two genes, c‐ Erb Aα and c‐ Erb Aβ, generate at least four TR isoforms in the rat: TRα 1 , c‐erbAα 2 , TRβ 1 , and TRβ 2 . Although functional TRs have been identified in cells of the osteoblast lineage, it is still not known if TR isoform expression in bone differs depending upon which skeletal site is examined. We have used ribonuclease protection assay and Northern blot analysis to simultaneously examine the expression of TR isoform mRNAs in adult rat femoral and vertebral bone. TRα 1 , c‐erbAα 2 , and TRβ 1 are expressed in both femur and vertebra whole bone. Bone marrow cells from both skeletal sites were also cultured under conditions whereby the osteoprogenitors differentiated into osteoblasts and formed a mineralized extracellular matrix. TRα 1 , c‐erbAα 2 , and TRβ 1 mRNAs are each expressed in both femoral and vertebral osteoblast cultures. The presence of TRα 1 , c‐erbAα 2 , and β 1 proteins was confirmed by Western analysis of nuclear protein extracts from femoral and vertebral cell cultures. These results indicate that the three predominant TR isoforms are highly expressed in bone and osteoblasts from femurs and vertebrae. Whether there are distinct mechanisms of thyroid hormone action mediated by TRα 1 , c‐erbAα 2 , and TRβ 1 at these separate skeletal sites remain to be shown. J. Cell. Biochem. 74:684–693, 1999. © 1999 Wiley‐Liss, Inc.