胰岛素硫酸盐在慢性脏病中通过铁灭亡加剧了膜骨损失
Huiwen Chen1,2, Yining Zhou1,2, Yingli Liu3
1Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Oral diseases
|June 27, 2024
概括
内氧硫酸盐 (IS) 通过激活AhR通路并诱导铁亡,导致骨质生成受损,加剧慢性病 (CKD) 中的膜骨损失.
科学领域:
- 牙周病学和脏病学
- 生物化学和分子生物学
- 生物材料和组织工程
背景情况:
- 慢性病 (CKD) 与全身并发症有关,包括骨代谢受损.
- 硫酸 (IS),一种常见的尿素毒素,已与各种CKD相关的病理有关.
- 在CKD患者中,IS在膜骨损失中的特定作用尚未完全阐明.
研究的目的:
- 为了调查状骨质恶化中的硫酸 (IS) 的参与.
- 阐明慢性病 (CKD) 患者中膜骨损失的潜在机制.
主要方法:
- 动物模型:对照组,牙周炎 (CP),CKD和CKD+CP组.
- 生物化学分析:高性能液体色谱 (HPLC) 用于在牙裂液 (GCF) 中的IS度.
- 细胞和分子分析:IS刺激MC3T3-E1细胞以评估骨质分化,线粒体形态,铁亡标志物和信号通路 (AhR,SLC7A11/GPX4).
- 组织学分析:微计算机断层扫描 (micro-CT) 用于骨微架构的评估.
主要成果:
- 与其他组相比,CKD+CP组中膜骨破坏明显更严重.
- 在CKD小鼠的GCF中检测到升高的IS水平.
- 在体外,IS激活了基受体 (AhR),抑制了MC3T3-E1细胞的骨质分化,改变了线粒体形态,并激活了SLC7A11/GPX4通路.
- 抑制AhR减弱的IS诱导作用.
结论:
- 在慢性病 (CKD) 的背景下,基硫酸 (IS) 在加剧膜骨损失方面发挥着关键作用.
- 通过激活AhR/SLC7A11/GPX4信号通路,IS促进膜骨的再吸收,从而导致铁和抑制骨质生成.
- 向IS介导途径为治疗慢性病患者牙周并发症提供了潜在的治疗策略.
相关概念视频
01:29Bone Disorders
3.5K
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...
3.5K
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
01:11Renal Failure: Dose Adjustments
79
In patients with renal impairment, drugs undergo significant changes in their pharmacokinetics, which require dosage adjustments to ensure safe and effective therapy.
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
79
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
01:16Necrosis
4.4K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.4K
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