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Thyroid-stimulating hormone maintains bone mass and strength by suppressing osteoclast differentiation
Authors:Wenwen Zhang  Yanling Zhang  Yuantao Liu  Jie Wang  Ling Gao  Chunxiao Yu  Huili Yan  Jiajun Zhao  Jin Xu
Institution:1. Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province 250021, China;2. Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong Province 250021, China;3. Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong Province 250021, China;4. Department of Endocrinology, the Second Hospital of Shandong University, Jinan, Shandong Province 250033, China;5. Scientific Center, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province 250021, China
Abstract:It has been suggested that pituitary hormone might be associated with bone metabolism. To investigate the role of thyroid-stimulating hormone (TSH) in bone metabolism, we designed the present study as follows. After weaning, TSH receptor (TSHR) null mice (Tshr/) were randomly divided into a thyroxine treatment group (n=10) or non-treatment group (n=10); the treatment group received a dose of desiccated thyroid extract at 100 ppm daily for 5 weeks. Age-matched wild-type (Tshr+/+, n=10) and heterozygote mice (Tshr+/, n=10) served as controls. After 5 weeks, the animals were sacrificed, and the femurs were collected for histomorphometrical and biomechanical analyses. In addition, the effect of TSH on osteoclastogenesis was examined in the RAW264.7 osteoclast cell line. We found that compared with Tshr+/+ mice, Tshr/ and Tshr+/ mice had lower bone strength. The histomorphometric results showed that trabecular bone volume, osteoid surface, osteoid thickness and osteoblast surface were significantly decreased, whereas the osteoclast surface was significantly increased in both Tshr/ and Tshr+/ mice compared with Tshr+/+ mice. Bone resorption and formation in Tshr/ mice were further enhanced by thyroxine replacement. bTSH inhibited osteoclast differentiation in vitro, as demonstrated by reduced development of TRAP-positive cells and down-regulation of differentiation markers, including tartrate-resistant acid phosphatase, matrix metallo-proteinase-9 and cathepsin K in RAW264.7 cells. Our results confirm that TSH increased bone volume and improved bone microarchitecture and strength at least partly by inhibiting osteoclastogenesis.
Keywords:TSH  Bone metabolism  TSHR-null mice  Osteoclast
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