相关实验视频

Updated: May 15, 2025

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

单细胞转录组分析显示,AP-1的下调调节重塑了骨髓环境,并导致卵巢切除小鼠的骨质疏松症

Zhanrong Zhang¹, Zhengbo Tao¹, Zheng Zhang^1,2

¹Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai, China.

Journal of orthopaedic translation

|April 11, 2025

概括

雌激素缺乏会破坏骨髓免疫力,导致骨质疏松症. 抑制激活蛋白1 (AP-1) 或B细胞增殖为这种疾病提供了潜在的治疗策略.

科学领域:

免疫学免疫学免疫学
内分泌学在内分泌学.
骨生物学骨生物学骨生物学

背景情况:

雌激素缺乏引起的骨质疏松症源于骨髓免疫微环境的改变.
精确的细胞和分子机制,包括激活蛋白1 (AP-1) 的作用,尚未完全理解.
研究AP-1在调节骨髓组成和骨质细胞形成中的作用至关重要.

研究的目的:

阐明雌激素缺乏如何影响骨髓细胞组成和信号通路.
确定AP-1在雌激素缺乏引起的骨损失中的调节作用.
探索针对AP-1和B淋巴发生的治疗潜力.

主要方法:

单细胞RNA测序 (scRNA-seq) 分析了模拟手术和卵巢切除 (OVX) 的小鼠的骨髓细胞.
在体内使用抑制剂T5224和体内通过雌激素受体信号传递验证了AP-1的功能.
在OVX小鼠中使用IL-7单克隆抗体抑制B淋巴发生.

主要成果:

OVX小鼠的B细胞增殖和中性粒细胞减少,反映了AP-1抑制的效果.
在OVX小鼠中,scRNA-seq揭示了在多种细胞类型中AP-1亚单元的减少表达.
抑制AP-1促进了B细胞增殖和骨质细胞生成因子 (GM-CSF,RANKL);IL-7阻断减轻了骨质损失.

结论:

降低AP-1的调节有助于因雌激素缺乏而导致的骨质疏松症,通过破坏骨髓平衡,促进B细胞扩张.
由B细胞增殖驱动的骨质细胞信号的升高,加剧了骨质损失.
用IL-7阻断向B细胞增殖是一种有前途的治疗方法,用于治疗雌激素缺乏性骨质疏松症.

关键词:

AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 AP-1 B 细胞 B 细胞雌激素缺乏症雌激素缺乏症骨质疏松症是一种骨质疏松症.进行卵巢切除术.

更多相关视频

A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders

A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders

Published on: June 8, 2014

Osteoclast Derivation from Mouse Bone Marrow

Osteoclast Derivation from Mouse Bone Marrow

Published on: November 6, 2014

相关概念视频

Osteoclasts in Bone Remodeling

Osteoclasts in Bone Remodeling

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...

Bone Remodeling

Bone Remodeling

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.