相关实验视频

Updated: May 12, 2025

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

针对PRC1.1复合物的有针对性的干扰增强了骨重塑

Liangyu Xing^1,2, Jinxin Xu^3,4, Meihan Gong^1,2

¹State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Key Laboratory of Medical Epigenetics, Department of Endodontics, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, Tianjin Medical University, Tianjin, China.

Nature communications

|May 9, 2025

概括

聚合物抑制复合物1.1 (PRC1.1) 通过抑制Wnt信号来抑制骨的形成. 抑制PRC1.1活动可以增强骨重塑,并为骨恶化提供治疗策略.

科学领域:

表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
骨生物学骨生物学骨生物学
分子医学是分子医学.

背景情况:

多镇压复合体 (PRCs) 是维持细胞身份的关键表观遗传调节体.
对于PRCs,特别是PRC1.1在骨质母细胞功能和骨形成中的特定作用还不清楚.
衰老与改变的表观遗传景观有关,可能会影响骨健康.

研究的目的:

研究PRC1.1在骨质母细胞功能和骨形成中的作用.
确定PRC1.1影响骨重塑的分子机制.
探索针对骨质损失条件的PRC1.1的治疗策略.

主要方法:

对老化骨质母细胞中PRC1.1激活的分析.
染色体免疫沉用于识别PRC1.1结合因子 (KDM2B,BCOR,PCGF1).
产生骨质细胞特异性Kdm2b淘汰小鼠.
开发一种针对PRC1.1.1.的小分子抑制剂 (iBP).
在小鼠模型中评估骨重塑和Wnt信号.

主要成果:

在衰老的骨质母细胞中,PRC1.1被激活,KDM2B,BCOR和PCGF1调解H2A单双化 (H2AK119ub1).
骨质细胞特异的Kdm2b无活化通过降低H2AK119ub1的调节和激活Wnt信号来促进骨重塑.
小分子IBP有效抑制PRC1.1的活性.
在骨损失的小鼠模型中,iBP的使用增强了骨的形成.

结论:

PRC1.1作为骨形成的关键表观遗传制动作用.
通过抑制BCOR-PCGF1相互作用来准PRC1.1,增强了Wnt通路的激活.
治疗抑制PRC1.1是一种有前途的策略,可以对抗骨恶化和骨质损失.

更多相关视频

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model

Published on: July 3, 2020

Author Spotlight: Comparing Alveolar and Long Bone Remodeling to Explore OTM Model Potential

Author Spotlight: Comparing Alveolar and Long Bone Remodeling to Explore OTM Model Potential

Published on: July 21, 2023

相关概念视频

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.

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...