| Objective:By studying the differents of bone biomechanics and histormorphometry in thyroid stimulating hormone receptor (TSHR) gene knockout mice, and exploring the effects of different doses of thyroid-stimulating hormone (TSH) on osteoclast differentiation process and related gene expression, to investigate the role of TSH in bone metabolism, and the possible mechanisms underlying.Methods:TSHR null mice (Tshr-/-) after weaned were randomly divided into thyroxine treatment group (n=10) or untreatment group (n=10); the treatment group received a dose of100ppm desiccated thyroid extract daily orally. Age-matched wild type (Tshr+/+, n=10) and heterozygote mice (Tshr+/-, n=10) were used as controls. After8weeks, the animals were sacrificed, and the femurs were collected for histomorphometric and biomechanical analyses. In addition, RAW264.7cells were induced to differentiate into osteoclasts by addition of ligand of receptor activator of NF-κB (RANKL), and treated without or with different doses of TSH. The effects of TSH on osteoclastogenesis and related gene expression were also examined.Results:Compared with Tshr+/+mice, the bone strength was significantly decreased in both Tshr-/-and Tshr+/-mice. Results of the histomorphometrical studies showed that decreased trabecular bone volume, osteoid surface, osteoid thickness, osteoblast surface, and a significant increase in osteoclast surface in Tshr-/-and Tshr+/-mice as well. In vitro studies suggest that TSH inhibited osteoclastogenesis as evidenced by decreased development of TRAP-positive cells, and by decreased expression, in a concentration-dependent manner, of osteoclast differentiation markers, including tartrate-resistant acid phosphatase, matrix metallo-proteinase-9and cathepsin K.Conclusion:TSH can suppress osteoclast differentiation and function, which may be part mechanism of the TSH inhibiting bone resorption and maintaining bone mass, bone structure and strength. |
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