FOXC1通过Dnmt3b/CXCL12轴促进骨髓中介细胞的骨质细胞分化
Peiguang Zhang1, Bo Feng1, Guangming Dai1
1Department of Orthopedics, The Third Affiliated Hospital, Inner Mongolia Medical University, No. 20 Shaoxian Road, Kundulun District, Baotou, 014010, Inner Mongolia, People's Republic of China.
Biochemical genetics
|June 12, 2023
概括
FOXC1通过Dnmt3b/CXCL12通路增强骨髓介质干细胞 (BM-MSC) 骨质分化,减少炎症和改善骨折愈合,促进骨缺陷修复.
科学领域:
- 整形外科 整形外科 整形外科
- 干细胞生物学 干细胞生物学
- 分子生物学分子生物学
背景情况:
- 骨缺陷在骨科中是一个重大挑战.
- 骨髓介质干细胞 (BM-MSCs) 在骨再生方面表现有前途.
- 了解调节BM-MSC骨质分化的分子机制至关重要.
研究的目的:
- 调查FOXC1在调节BM-MSC骨质分化的作用.
- 为了阐明涉及FOXC1,Dnmt3b和CXCL12在骨修复中的分子途径.
- 在临床前模型中评估FOXC1的治疗潜力.
主要方法:
- 骨缺陷的体外和体外模型.
- 性酸酶和阿利沙林红色染色用于骨质分化.
- 西部涂抹,ELISA,HE染色用于分子和组织学分析.
- 双化酶报告员,甲基化特异性PCR和ChIP测试以确定分子相互作用.
主要成果:
- 过度表达FOXC1增强了骨质分化,并减少了BM-MSCs中的炎症.
- 在体内,FOXC1促进了骨折愈合,并降低了CXCL12的调节.
- FOXC1的目标是Dnmt3b,这反过来又调节了Dnmt3b/CXCL12轴.
- Dnmt3b的淘汰和CXCL12的过度表达损害了FOXC1介导的骨质生成差异化.
结论:
- FOXC1-Dnmt3b-CXCL12轴是BM-MSC骨质分化的关键调节器.
- 通过调节这一轴,FOXC1促进骨修复,提供潜在的治疗点.
相关概念视频
01:19Mesenchymal Stem Cells
4.8K
Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
4.8K
01:31Osteoclasts 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
02:23Master Transcription Regulators
7.0K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.0K
01:30Bone Cells and Tissue
4.8K
Bones contain a relatively small number of cells entrenched in a matrix of organic and inorganic components. Although bone cells compose only a small amount of the bone volume, they are crucial to its function. Four types of cells are found within the bone tissue— osteoblasts, osteocytes, osteogenic cells, and osteoclasts.
Osteoblasts and Osteocytes
The osteoblast is the bone cell responsible for forming new bone tissue. It is found in the growing portions of bone, including the...
Osteoblasts and Osteocytes
The osteoblast is the bone cell responsible for forming new bone tissue. It is found in the growing portions of bone, including the...
4.8K
01:24Bone Formation by Endochondral Ossification
4.8K
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...
4.8K