THE ISOFORM-SPECIFIC EXPRESSION OF THE TRIIODOTHYRONINE RECEPTOR IN OSTEOBLASTS AND OSTEOCLASTS

Hyperthyroidism is associated with an increase in both osteoblast and osteoclast activity. We have previously shown that, in vitro, osteocla sts do not respond directly to tri-iodothyronine to increase bone reso rption but that the effect is mediated by another bone cell, probably the osteoblast. To investigate this issue further we have studied the isoform-specific expression of thyroid receptor (TR) protein in human osteoclasts derived from an osteoclastoma (giant cell tumour of bone) and the expression of TR mRNA and protein in the osteoblastic cell lin es MG 63 and UMR 106. Three major TR receptor variants have been descr ibed; TR alpha 1 and TR beta are functional receptors whereas c-erbA a lpha 2 is a non-functional variant. Northern blot analysis using [P-32 ]- cDNA probes against human TR alpha 1, c-erbA alpha 2 and TR beta de monstrated specific binding of these probes to mRNA from MG 63 and UMR 106. mRNA for all three receptor variants was observed in both cell l ines, in UMR 106 multiple mRNA transcripts were present for TR alpha 1 and TR beta. Immunohistochemical staining with antibodies recognizing a common TR alpha epitope and specific c-erbA alpha 2 and TR beta epi topes extended these observations by demonstrating receptor protein in both osteoblasts and osteoclasts. These findings are consistent with previous observations of TR expression in osteoblast-like cells and ar e the first direct demonstration of TR in osteoclasts.