缺氧,质和骨关节炎:解开分子交叉语音的关系
Zhanliang Jiang1, Jin Li2, Mingpeng Shi3
1Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130000, Jilin Province, China; College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, Jilin Province, China.
Redox biology
|July 16, 2025
概括
增加的氧气通过诱导铜亡,一种依赖铜的细胞死亡来加速骨关节炎. 稳定缺氧诱导因子-1α (HIF-1α) 提供了保护,为OA治疗提供了新的治疗点.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 病理学 病理学 病理学
背景情况:
- 骨关节炎 (OA) 的发展与缺氧微环境的变化有关.
- 铜,一种依赖铜的调节细胞死亡,受氧含量的影响.
- 缺氧,亡和OA病原体之间的相互作用尚未完全理解.
研究的目的:
- 为了研究氧气水平,cuproptosis和骨关节炎进展之间的关系.
- 阐明将氧化与状细胞死亡和OA联系起来的分子机制.
- 评估缺氧诱导因子-1α (HIF-1α) 在OA和cuproptosis中的作用.
主要方法:
- 利用OA模型来评估氧气水平的变化,基因表达和冠状细胞活力.
- 研究了铜载体 (SLC31A1,ATP7B) 和DLAT寡合化的表达.
- 使用siRNA和稳定技术检查了HIF-1α,DLAT,OA严重程度和状细胞对cuproptosis的反应之间的相关性.
主要成果:
- 在OA进展过程中,氧气水平会增加,抑制合成代谢基因,并在关节软骨中调高合成代谢基因.
- 升高的氧气通过上调SLC31A1和下调ATP7B来促进铜的积累,导致DLAT寡合化和cuproptosis.
- HIF-1α表达与DLAT和OA严重程度有负相关性; HIF-1α沉默会加剧cuproptosis,而稳定是保护性的.
结论:
- 软骨中增加的氧气会诱导亡,加速OA的进展.
- HIF-1α稳定减轻了氧气诱导的亡,并可能对OA产生保护作用.
- 准氧气水平和HIF-1α通路为骨关节炎提供了潜在的治疗策略.
相关概念视频
01:31Osteoclasts in Bone Remodeling
3.2K
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...
3.2K
01:24Regulation of Angiogenesis and Blood Supply
2.7K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.7K
01:23Hypoxia
1.2K
Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
1.2K
02:53Adaptive Mechanisms in Cancer Cells
5.9K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.9K
01:24Bone Formation by Endochondral Ossification
5.5K
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...
5.5K
01:20COPD: Pathogenesis and Clinical Features
531
Chronic obstructive pulmonary disease (COPD) is a group of lung conditions that progressively worsen over time, including chronic bronchitis and emphysema. This cluster of diseases collectively leads to a gradual and irreversible decline in lung function over time.
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
531