TRα1 and TRβ1 are expressed in growth plate chondrocytes, bone marrow stromal cells, and osteoblasts but it is uncertain whether they are present in osteoclasts. Expression of TRα1 is around ten times higher than TRβ1 in bone, suggesting the major T3 actions in bone are mediated via TRα1. Osteoblasts, osteoclasts, and chondrocytes also express thyroid hormone transporters to regulate local availability of thyroid hormone within bone.
In vivo and in vitro studies have shown that T3 acts to inhibit growth plate chondrocyte proliferation and stimulate hypertrophic chondrocyte differentiation. In childhood hypothyroidism, growth arrest and delayed bone formation are consequences of gross disruption of growth plate architecture (epiphyseal dysgenesis) and a failure of hypertrophic chondrocyte differentiation. By contrast thyroid hormone excess accelerates chondrocyte differentiation resulting in advanced bone formation.
In osteoblasts, T3 increases proliferation and differentiation via complex cytokine and growth factor signalling pathways. For ex ample, T3 induces FGFR1 in osteoblasts. Consistent with this, activating mutations of FGFR1 cause Pfeiffer’s craniosynostosis syn drome, and craniosynostosis is a recognized manifestation of severe juvenile thyrotoxicosis. Thyroid hormone also stimulates osteoclast proliferation and activity, but it is uncertain whether this is a direct cellular response to T3.
The TSH receptor is expressed on osteoblasts, chondrocytes, and osteoclasts, however TSHα/ β expression has not been detected within bone. Direct actions of TSH on bone are uncertain. TSH may either inhibit or have no effect upon osteoclast differentiation, promote or have no effect upon osteoblast differentiation and promote chondrocyte differentiation.
