通过CUL4A介导的ZEB1/microRNA-340-5p/HMGB1轴促进了骨质疏松症的发展
Hongliang Chen1, Qiang Zheng1, You Lv1
1Department of Joint Surgery, Shenyang Sujiatun District Central Hospital, Shenyang, China.
Journal of biochemical and molecular toxicology
|May 30, 2023
概括
库林4A (CUL4A) 促进骨质疏松症,通过增加指 E-box 结合 homeobox 1 (ZEB1) 表达,抑制 miR-340-5p,导致骨质细胞分化和骨质损失.
科学领域:
- 分子生物学分子生物学
- 骨生物学 骨生物学
- 骨质疏松症的细胞机制
背景情况:
- 骨质疏松症是与骨质损失相关的重大健康问题.
- 库林4A (CUL4A) 在骨质细胞分化和骨质疏松症中的作用尚不清楚.
- 了解这些机制对于开发有针对性的疗法至关重要.
研究的目的:
- 研究CUL4A在骨质细胞分化和骨质疏松症中的作用.
- 阐明涉及CUL4A,ZEB1,miR-340-5p,HMGB1和TLR4在骨质疏松症发展中的分子途径.
主要方法:
- 使用双边卵巢切除术 (OVX) 开发了一种骨质疏松症的小鼠模型.
- 在OVX小鼠骨髓中评估CUL4A表达.
- 利用生物信息分析,基因转移和ChIP测试来研究分子相互作用.
- 研究了改变骨髓巨细胞 (BMM) 中CUL4A,ZEB1,miR-340-5p和TLR4表达的效应.
主要成果:
- 在OVX小鼠中,CUL4A表达升高,促进骨质细胞分化.
- 击败CUL4A缓解了骨质疏松症的症状.
- 过度表达CUL4A通过H3K4me3甲基化增加了ZE1的表达.
- ZEB1抑制了miR-340-5p,上调了HMGB1,并激活了TLR4通路,导致骨质细胞分化和骨质疏松症.
结论:
- CUL4A在促进骨质细胞分化和骨质疏松症方面发挥着关键作用.
- CUL4A/ZEB1/miR-340-5p/HMGB1/TLR4轴是骨质疏松病变发生的关键途径.
- 准这种途径可能为骨质疏松症提供治疗策略.
相关概念视频
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
01:40Bone Remodeling
38.4K
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.
38.4K
01:17Hormones and Bone Tissue
2.8K
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...
2.8K
01:29Bone Disorders
3.7K
Aging and its effect on bone remodeling is the most common cause of bone disorders. In young and healthy people, bone deposition and resorption happen at an equal rate to maintain optimal bone health.
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
3.7K
01:31Essential Minerals for Bone Health
4.2K
The minerals contained in all of the food we consume are essential for our organ systems. However, certain essential minerals, such as calcium, phosphorus, magnesium, manganese, and fluoride, largely affect bone health.
Calcium and Phosphorus
Calcium is a critical component of bones, especially in the form of calcium phosphate and calcium carbonate. Since the body cannot make calcium, it must be obtained from the diet. However, calcium cannot be absorbed from the small intestine without...
Calcium and Phosphorus
Calcium is a critical component of bones, especially in the form of calcium phosphate and calcium carbonate. Since the body cannot make calcium, it must be obtained from the diet. However, calcium cannot be absorbed from the small intestine without...
4.2K
01:25Role of Vitamins in Maintaining Bone Health
3.5K
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...
3.5K