The Localization of Thyroid Hormone Receptor mRNAs in Human Bone

Thyroid hormones have well-documented effects on the skeleton although the mechanism of their action on bone is poorly understood. We have recently reported the presence of different thyroid hormone receptor isoforms in human bone. However, there is evidence to suggest that the expression of thyroid hormone receptor (TR) protein may not necessarily correlate with its mRNA. In this study, we used specific digoxigenin-labeled ribo probes to investigate the expression of TRαl, variant TRα2, TRβ31, and in particular TRβ32 mRNA in human osteophytic bone and osteoclastoma tissue in situ. The number of positive cells was expressed as the percentage of the total number of cells of the same phenotype. In osteophytes, at sites of endochondral ossification, TRαl, variant TRα2, TRβ31, and TRα32 mRNA were widely distributed in undifferentiated, proliferating, mature and hypertrophie chondrocytes. At sites of bone remodeling, TRal mRNA was expressed in the majority (< 90%) of osteoblasts. TRβ31 and the variant TR-α2 mRNA were moderately expressed in approximately 75% of cells with only a few osteoblasts (> 25%) expressing TRβ32 mRNA. All the TR transcripts were highly expressed in multinucleated osteoclasts in osteoclastoma tissue. The distribution of TR mRNAs was similar to TR receptor protein expression (as we have previously reported) in both osteophytic bone and osteoclastoma tissue except TRαl mRNA that was highly expressed in osteoclasts and in undifferentiated, proliferating, mature, and hypertrophie chondrocytes in contrast to its receptor protein expression. This study highlights the importance of studying both TR mRNA and receptor proteins in triiodothyronine (T₃) responsive tissues. This is also the first demonstration of the presence of TRβ32 mRNA in bone. The role of TRβ32 in mediating the actions of thyroid hormones in bone is not known and requires further investigation.