在青少年异常性关节炎中,骨周转的分子调节:动物模型,细胞特征和TNFα
Harry C Blair1, Jonathan Soboloff2, Irina L Tourkova1
1Departments of Pathology and of Cell Biology, The Pittsburgh VA Medical Center and the University of Pittsburgh, Pittsburgh, PA 15261, USA.
Frontiers in bioscience (Landmark edition)
|July 31, 2024
概括
瘤坏死因子-α (TNFα) 在炎症性关节炎中驱动异常的骨周转,导致骨质损失. 针对TNFα和相关通路,包括TRPC通道,为早期干预提供了有前途的治疗策略.
科学领域:
- 类风湿病学 类风湿病学
- 免疫学 免疫学 免疫学
- 骨生物学 骨生物学 骨生物学
背景情况:
- 炎症性关节炎,包括类风湿性关节炎,以异常的骨周转和骨损失为特征.
- 瘤坏死因子-α (TNFα) 在炎症性关节炎和骨再吸收的发病过程中起着中心作用.
研究的目的:
- 审查与TNFα相关的机制,这些机制有助于在异常性炎症性和类风湿性关节炎中减轻骨质损失.
- 讨论青少年无形性关节炎和相关的小鼠模型.
- 突出涉及TRPC通道在骨再吸收细胞分化中的新奇机制.
主要方法:
- 对人类自身性关节炎的数据的审查,特别是在青少年患者中.
- 对类风湿性关节炎小鼠模型的分析,重点关注TNFα和RANKL.
- 在体外和小鼠模型研究中,研究了TRPC通道参与骨再吸收.
主要成果:
- 在人类和动物模型中,关节中的巨细胞会降解骨和软骨.
- 在类风湿性关节炎模型中,TNFα表达与骨再吸收细胞有很强的相关性.
- 在炎症性关节炎中,TRPC通道参与了骨再吸收细胞的分化.
结论:
- 针对TNFα等炎症性细胞因子的早期检测和干预至关重要,特别是在青少年关节炎中.
- 针对疾病媒介细胞因子的单克隆抗体显示出治疗潜力.
- TRPC通道抑制剂代表了炎症性关节炎的新疗法.
相关概念视频
The JAK-STAT Signaling Pathway
8.8K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.8K
T Cell Types and Functions
967
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
967
TGF - β Signaling Pathway
7.3K
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...
7.3K
Bone Remodeling
38.2K
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.
38.2K
Osteoclasts in Bone Remodeling
2.9K
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...
2.9K


