是一种对葡萄糖皮质激素的低亲和度受体,对于葡萄糖皮质激素诱导的骨损失是必需的
Wenyu Fu1,2, Meng Chen2, Kaidi Wang2
1Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, USA.
Cell research
|January 1, 2025
概括
研究人员发现作为一种新的葡萄糖皮质体 (GC) 受体,对GC诱导的骨质疏松症 (GIO) 至关重要. 用TRx0237抑制Tau可以防止GIO,提供了一种减轻GC副作用的策略.
科学领域:
- 内分泌学和药理学 在内分泌学和药理学
- 骨生物学和疾病
背景情况:
- 葡萄糖皮质醇 (GCs) 是广泛使用的抗炎和免疫抑制药物.
- GCs引起显著的副作用,包括GC诱导的骨质疏松症 (GIO),其机制尚不清楚.
- 了解GIO机制对于改善GC疗法至关重要.
研究的目的:
- 确定参与GC诱导骨质疏松症 (GIO) 的新型受体.
- 调查Tau在GC行动和GIO中的作用.
- 评估Tau抑制作为针对GIO的治疗策略.
主要方法:
- 鉴定tau作为一个低亲和度的GC结合受体.
- 在关节炎和GIO模型中对德甲诱导的骨损失对Tau缺乏的影响的评估.
- 对一种tau抑制剂 (TRx0237) 在预防GIO方面进行评估.
主要成果:
- 陶缺乏症显著地保护了德克萨米他诱导的骨损失.
- 抑制剂TRx0237有效地预防了GIO.
- 结合TRx0237和德克萨治疗克服了德克萨在炎症性关节炎中的骨质疏松副作用.
结论:
- 是一种以前未被识别的GCs低亲和度受体,在GIO中发挥关键作用.
- 向TAU提供了一种有希望的策略来缓解与GC相关的骨质疏松症.
- 用GC和Tau抑制剂进行组合治疗可能会改善GC治疗的安全性.
相关概念视频
Osteoclasts in Bone Remodeling
2.8K
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...
2.8K
Hormones and Bone Tissue
2.6K
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...
2.6K
Bone Remodeling
38.1K
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.
38.1K
Transducer Mechanism: Nuclear Receptors
1.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K


