TSH is a negative regulator of skeletal remodeling
TSH is a negative regulator of skeletal remodeling
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DOI：
10.1016/s0092-8674(03)00771-2
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发表时间：
2003-10-17
期刊：
影响因子：
64.5
通讯作者：
Zaidi, M
中科院分区：
文献类型：
--
作者：
Abe, E;Marians, RC;Zaidi, M
促甲状腺激素（TSH）的既定功能是促进甲状腺滤泡发育和激素分泌。传统上，与甲状腺功能亢进相关的骨质疏松症被视为甲状腺功能改变的继发后果。我们提供了 TSH 对骨骼重塑、成骨细胞骨形成和破骨细胞骨吸收的直接影响的证据，这是通过成骨细胞和破骨细胞前体上发现的 TSH 受体 (TSHR) 介导的。即使 TSHR 表达减少 50%，也会导致严重的骨质疏松（骨丢失）和局灶性骨硬化（局部骨形成）。 TSH 通过减弱响应 RANK-L 和 TNFα 触发的 JNK/c-jun 和 NFkappaB 信号传导来抑制破骨细胞形成和存活。 TSH 还通过下调 Wnt (LRP-5) 和 VEGF (Flk) 信号传导，以独立于 Runx-2 和 osterix 的方式抑制成骨细胞分化和 1 型胶原蛋白表达。这些研究将 TSH 定义为独立控制骨形成和骨吸收的单分子开关。
The established function of thyroid stimulating hormone (TSH) is to promote thyroid follicle development and hormone secretion. The osteoporosis associated with hyperthyroidism is traditionally viewed as a secondary consequence of altered thyroid function. We provide evidence for direct effects of TSH on both components of skeletal remodeling, osteoblastic bone formation, and osteoclastic bone resorption, mediated via the TSH receptor (TSHR) found on osteoblast and osteoclast precursors. Even a 50% reduction in TSHR expression produces profound osteoporosis (bone loss) together with focal osteosclerosis (localized bone formation). TSH inhibits osteoclast formation and survival by attenuating JNK/c-jun and NFkappaB signaling triggered in response to RANK-L and TNFalpha. TSH also inhibits osteoblast differentiation and type 1 collagen expression in a Runx-2- and osterix-independent manner by downregulating Wnt (LRP-5) and VEGF (Flk) signaling. These studies define a role for TSH as a single molecular switch in the independent control of both bone formation and resorption.