title: Thyroid-stimulating hormone maintains bone mass and strength by suppressing osteoclast differentiation.
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.
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province 250021, China; Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong Province 250021, China; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong Province 250021, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province 250021, China; Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong Province 250021, China; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong Province 250021, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, the Second Hospital of Shandong University, Jinan, Shandong Province 250033, China.
authors.forename: Yuantao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province 250021, China; Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong Province 250021, China; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong Province 250021, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province 250021, China; Scientific Center, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province 250021, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province 250021, China; Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong Province 250021, China; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong Province 250021, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province 250021, China; Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong Province 250021, China; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong Province 250021, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province 250021, China; Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong Province 250021, China; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong Province 250021, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong Province 250021, China; Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, Shandong Province 250021, China; Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong Province 250021, China. Electronic address: xujin@medmail.com.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D015519:Bone Density; D001862:Bone Resorption / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D005269:Femur / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology*; D013961:Thyroid Gland / Q000737:chemistry; D013972:Thyrotropin / Q000502:physiology*; D013974:Thyroxine / Q000008:administration & dosage
chemical_list: D013972:Thyrotropin; D013974:Thyroxine
keywords: Bone metabolism; Osteoclast; TSH; TSHR-null mice