甲状腺激素受体Thra和Thrb淘汰赛在体外对骨质母细胞生物学和甲状腺激素响应有不同的影响
Franziska Lademann1, Elena Tsourdi1, Lorenz C Hofbauer1
1Department of Medicine III and University Center for Healthy Aging, Technische Universität Dresden Medical Center, Dresden, Germany.
Journal of cellular biochemistry
|November 22, 2023
概括
甲状腺激素受体α1 (TRα1) 和β1 (TRβ1) 不同调节骨细胞. TRα1淘汰会增强骨质细胞活性,而TRβ1对骨中的甲状腺激素信号至关重要.
科学领域:
- 内分泌学 在内分泌学.
- 骨生物学 骨生物学 骨生物学
- 分子内分泌学分子内分泌学
背景情况:
- 甲状腺激素 (TH) 对骨重塑至关重要,甲状腺功能障碍会损害骨健康.
- 甲状腺激素受体 (TR),特别是TRα1和TRβ1,调解TH的作用.
- 之前的研究表明,TRα1是骨TH效应的主要媒介.
研究的目的:
- 在细胞水平上研究TRα1和TRβ1在骨质母细胞中的不同作用.
- 确定TR淘汰赛如何影响骨质细胞分化,活性和对TH的反应.
- 阐明TR亚型在介导TH诱导的骨重塑标记物变化的特定贡献.
主要方法:
- 从缺乏TRα1 (Thra0/0) 和TRβ1 (Thrb-/-) 的小鼠及其野生型 (WT) littermates中分离出初级骨质母细胞.
- 骨质细胞分化,活性,矿化和基因表达在体外被评估.
- 在TR缺乏和WT骨质母细胞中评估了TH反应.
- 通过使用骨质母细胞的条件介质和测量骨质母细胞标记物基因表达来评估骨质母细胞发生.
主要成果:
- 与WT相比,TRα1淘汰赛 (Thra0/0) 显著增加了骨质细胞分化和活性.
- TRβ1淘汰赛 (Thrb-/-) 损害了骨质母细胞对TH的反应能力,包括矿化和基因表达.
- 骨质细胞表现出降低的RANKL/OPG比率,导致骨质细胞形成减少.
- 对WT骨质细胞的TH治疗增加了RANKL/OPG比率,并通过TRβ1间接刺激骨质细胞,这种效应在Thrb骨质细胞中减弱.
结论:
- 在体外,TRα1和TRβ1在调节骨质母细胞功能和TH反应方面发挥着不同的作用.
- TRα1淘汰赛增强了骨质母细胞的活性和分化,独立于TH.
- TRβ1对于介导TH对骨质母细胞活动,矿化和骨质母细胞生成的间接调节的影响至关重要.
相关概念视频
01:18Functions of Thyroid Hormones
2.8K
The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...
2.8K
01:17Hormones and Bone Tissue
2.7K
The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
2.7K
01:20Synthesis and Regulation of Thyroid Hormones
4.6K
Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
4.6K
01:31Osteoclasts in Bone Remodeling
3.0K
Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
3.0K
01:22Target Cell Response to Hormones
3.1K
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
3.1K
01:40Bone Remodeling
38.3K
Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
38.3K