血统可塑性和信号失调定义了骨关节炎进展的细胞轨迹
Guanghao Chen1, Kundi Tai2, Guoyu Dai3
1Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, 1518 North Huancheng Road, Jiaxing, 314000, People's Republic of China.
Clinical and experimental medicine
|November 25, 2025
概括
骨关节炎 (OA) 涉及细胞系可塑性和信号通路失调. 关键调节器HIF1A和ANGPTL4驱动细胞外基质降解,为OA提供新的治疗点.
科学领域:
- 生物医学科学 生物医学科学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 骨关节炎 (OA) 的特点是渐进的关节损伤.
- 了解OA中的细胞可塑性和信号传递对于有效治疗至关重要.
研究的目的:
- 探索OA进展中的细胞系变化.
- 为了确定信号通路失调和新分子点OA治疗.
主要方法:
- 单细胞RNA测序 (sc-RNAseq) 用于高分辨率的细胞谱系分析.
- KEGG和GO丰富,用于功能重编程的伪时间轨迹分析.
- 在体外实验用于候选基因验证.
主要成果:
- 在OA关节软骨中,表现出与PreFC,FC和PreHTC细胞子集的转录异质性.
- 在低氧和代谢重编程下,PreFC细胞经历转化为FC细胞.
- 确定HIF1A和ANGPTL4是OA中ECM降解,炎症和亡的关键调节者.
结论:
- 骨关节炎的进展涉及显著的细胞系可塑性,受信号通路失衡的影响.
- HIF1A和ANGPTL4是OA病变发生过程中的关键分子调节剂.
- 这项研究为OA提供了新的见解和潜在的治疗目标.
相关概念视频
Notch Signaling Pathway
6.4K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.4K
The JAK-STAT Signaling Pathway
11.8K
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...
11.8K
Bone Remodeling
40.2K
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.
40.2K
Bone Formation by Endochondral Ossification
8.3K
Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...
8.3K
Lineage Commitment
4.1K
Commitment is the process whereby stem cells:
4.1K
Diversity in Cell Signaling Responses
7.6K
The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity.
Graded and Abrupt Responses
Some signaling systems generate...
Graded and Abrupt Responses
Some signaling systems generate...
7.6K


