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 TR alpha 1, variant TR alpha 2, TR beta 1, and in particular TR beta 2 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, TR alpha 1, variant TR alpha 2, TR beta 1, and TR beta 2 mRNA were widely distributed in undifferentiated, proliferating, mature and hypertrophic chondrocytes. At sites of bone remodeling, TR alpha 1 mRNA was expressed in the majority (> 90%) of osteoblasts. TR beta 1 and the variant TR-alpha 2 mRNA were moderately expressed in approximately 75% of cells with only a few osteoblasts (< 25%) expressing TR beta 2 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 TR alpha 1 mRNA that was highly expressed in osteoclasts and in undifferentiated, proliferating, mature, and hypertrophic chondrocytes in contrast to its receptor protein expression. This study highlights the importance of studying both TR mRNA and receptor proteins in triiodothyronine (T-3) responsive tissues. This is also the first demonstration of the presence of TR beta 2 mRNA in bone. The role of TR beta 2 in mediating the actions of thyroid hormones in bone is not known and requires further investigation.