年轻的骨质细胞衍生的细胞外囊泡通过转移热胺-1促进骨质生成
Zhen-Xing Wang1,2,3, Xiao Lin4, Jia Cao1,2,3
1Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Journal of nanobiotechnology
|April 25, 2024
概括
年轻的骨质细胞衍生的细胞外囊泡 (YO-EVs) 促进骨形成,而衰老的骨质细胞衍生的EVs (SO-EVs) 在老化骨中促进脂肪形成. 含有托罗普米奥辛-1 (TPM1) 的YO-EV显示出对骨质疏松症的治疗潜力.
科学领域:
- 老年学是一门学科.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 老化骨髓介质干细胞 (BMSCs) 表现出骨质生成和脂肪生成的改变,导致骨密度降低和老年骨质疏松症中骨折风险增加.
- 骨细胞衰老在衰老过程中影响骨微环境和BMSC.
研究的目的:
- 研究骨细胞衰老对骨微环境的影响.
- 确定衰老过程中衰老骨质细胞对BMSCs的影响.
- 评估骨质细胞衍生的细胞外囊泡 (EVs) 在骨质疏松症中的治疗潜力.
主要方法:
- 从年轻和老老的小鼠中分离出初级骨细胞,以获得年轻的骨细胞衍生的EVs (YO-EVs) 和老化的骨细胞衍生的EVs (SO-EVs).
- 在实验室中评估了YO-EV和SO-EV对BMSC骨质生成和脂肪生成的影响.
- 利用转基因小鼠追踪骨质细胞衍生的EV分布,并观察骨质细胞的EV释放.
- 向年轻和年长的小鼠模型静脉注射YO-EV和SO-EV.
- 进行了蛋白质组学分析,以确定关键的EV组件,包括热胺-1 (TPM1).
主要成果:
- YO-EVs显著增强了BMSC性酸酶活性,矿化和骨质生成相关的基因表达.
- SO-EVs促进了BMSC脂肪生成,但没有影响骨质细胞生成.
- 静脉注射YO-EVs在小鼠模型中增加了骨质和生物力学强度.
- YO-EV治疗增加了骨质母细胞的数量,而SO-EV治疗增加了骨髓脂肪细胞.
- 在YO-EV中TPM1的丰富与增加的矩阵刚性和骨质生成有关;Tpm1的耗尽取消了YO-EV的骨质效应.
结论:
- YO-EVs对于维持骨形成和再吸收平衡至关重要,在衰老过程中,亲骨质性活性下降.
- 骨细胞衍生的EV,特别是YO-EV及其输送的TPM1,代表了老年骨质疏松症的有希望的治疗点.
相关概念视频
01:40Bone Remodeling
38.3K
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.
38.3K
01:31Osteoclasts 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
01:33Overview of Secretory Vesicles
8.5K
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
8.5K
01:30Bone Cells and Tissue
4.5K
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...
4.5K
01:17Hormones and Bone Tissue
2.7K
The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
2.7K
01:29The Extracellular Matrix
9.0K
Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
9.0K