环素D是线粒体透性过渡的调节剂,影响骨发育和骨折修复
Rubens Sautchuk1, John Martinez2, Sarah E Catheline1
1Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14624, USA.
Bone
|September 19, 2024
概括
赛克洛菲林D (CypD) 的功能获取突变通过破坏线粒体功能来损害骨发育和骨折愈合. 这突显了线粒体透性过渡孔 (MPTP) 在骨生长和修复中的作用.
科学领域:
- 线粒体生物学 线粒体生物学
- 骨生物学 骨生物学
- 细胞代谢的细胞代谢.
背景情况:
- 由cyclophilin D (CypD) 调节的线粒体透性过渡孔 (MPTP) 影响细胞氧化代谢,对干细胞分化至关重要.
- 以前的研究表明,Ppif基因 (编码CypD) 在骨质分化过程中被抑制,促进MPTP的关闭和加强骨质细胞中的线粒体代谢.
- CypD/MPTP调节与骨形态遗传蛋白 (BMP) 在衰老和骨折愈合中的信号相反相关,CypD功能增强 (GOF) 对骨维护产生负面影响.
研究的目的:
- 研究CypD功能增益 (GOF) 在成年小鼠骨发育,生长和骨折愈合中的功能作用.
- 提供功能性证据,将PPIF基因,CypD和MPTP与骨生长和修复过程联系起来.
主要方法:
- 使用了一种具有CypD功能的增益 (GOF) 的小鼠模型.
- 评估骨发育,生长速度和面骨和长骨中的骨化.
- 在骨折愈合后评估的骨体积.
主要成果:
- CypD GOF导致了面骨发育中的延迟骨化.
- 塞浦路斯GOF导致长骨的生长率下降.
- 骨折愈合受损,证据是CypD GOF小鼠骨结质体积减少.
结论:
- CypD的功能增长会对骨发育和生长产生负面影响.
- 在有效的骨折愈合中,CypD和MPTP起着至关重要的作用.
- 这些发现为PPIF基因与身高和骨矿物质密度等骨特征的关联提供了功能验证.
相关概念视频
01:25Role of Vitamins in Maintaining Bone Health
3.2K
The growth and maintenance of bone are regulated by a combination of nutritional factors, including vitamins, such as vitamin A, B12, C, D, and K.
Vitamin A
Vitamin A is involved in the process of bone remodeling. Retinoic acid, the active metabolite of Vitamin A, has nuclear receptors in osteoblasts and osteoclasts, which are involved in bone remodeling.
Vitamin B12
Vitamin B12 acts as a cofactor during the formation of osteoblast-related proteins, such as osteocalcin. Vitamin B12 plays a role...
Vitamin A
Vitamin A is involved in the process of bone remodeling. Retinoic acid, the active metabolite of Vitamin A, has nuclear receptors in osteoblasts and osteoclasts, which are involved in bone remodeling.
Vitamin B12
Vitamin B12 acts as a cofactor during the formation of osteoblast-related proteins, such as osteocalcin. Vitamin B12 plays a role...
3.2K
01:31Osteoclasts in Bone Remodeling
2.8K
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...
2.8K
01:40Bone 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
01:19Translocation of Proteins into the Mitochondria
3.1K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.1K
01:45Mitochondrial Membranes
9.2K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
9.2K
01:12Porin Insertion in the Outer Mitochondrial Membrane
2.9K
Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
2.9K