胆固醇硫酸盐通过调节AMPK-Sirt1-NF-κB通路来抑制骨质细胞分化和生存
Jin Ha Park1, Jiae Lee1, Gong-Rak Lee1
1Department of Life Science and the Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, Korea.
Journal of cellular physiology
|June 19, 2023
概括
胆固醇硫酸盐 (CS) 通过减少骨质细胞形成和促进细胞死亡来抑制骨质损失. 这独立于RORα,通过AMPK-Sirt1通路发生,突出显示CS是骨质疏松症的潜在治疗方法.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 胆固醇硫酸盐 (CS) 激活与视网膜酸相关的孤儿受体α (RORα).
- 众所周知,CS和RORα都在关节炎模型中减弱骨质结晶发生.
- 在骨质细胞分化中,CS和RORα的精确机制尚未完全理解.
研究的目的:
- 研究胆固醇硫酸盐 (CS) 和RORα在骨质细胞形成中的作用.
- 阐明参与CS介导的骨质细胞分化和生存调节的潜在分子机制.
主要方法:
- 在骨质细胞分化的体外研究.
- 在体内小鼠模型:原诱导的关节炎,脂多糖诱导的骨损失和卵巢切除诱导的骨损失.
- 西方斑点测试用于评估蛋白质酸化和乙化.
- 使用特定抑制剂 (AMPK 抑制剂) 和治疗方法 (互白素-1β).
主要成果:
- CS抑制了骨质细胞分化和诱导的亡,独立于RORα.
- CS增强了AMPK酸化和Sirt1活性,导致NF-κB抑制.
- 通过AMPK抑制剂逆转NF-κB抑制,证实了该途径.
- 在多个骨损失的小鼠模型中,CS证明了对骨损坏的保护作用.
结论:
- 胆固醇硫酸盐通过AMPK-Sirt1-NF-κB轴抑制骨质细胞分化和生存,独立于RORα.
- 骨骨显示出治疗炎症诱导的骨疾病和绝经后骨质疏松症的治疗潜力.
相关概念视频
Osteoclasts 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
NF-κB-dependent Signaling Pathway
7.5K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.5K
Cholesterol: Significance and Regulation
606
Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Considering cholesterol and...
606
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Hormones and Bone Tissue
2.8K
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...
2.8K
TGF - β Signaling Pathway
7.5K
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...
7.5K


