破骨细胞
骨重建
癌症研究
转录因子
化学
信号转导
染色质重塑
骨吸收
细胞生物学
髓样
染色质
医学
生物
内科学
生物化学
受体
基因
DNA
作者
Jiahui Du,Yili Liu,Xiaolin Wu,Jian Sun,Junfeng Shi,Hongming Zhang,Zheng Ao,Mingliang Zhou,Xinquan Jiang
标识
DOI:10.1038/s41467-023-37116-5
摘要
Bromodomain-containing protein 9 (BRD9), a component of non-canonical BAF chromatin remodeling complex, has been identified as a critical therapeutic target in hematological diseases. Despite the hematopoietic origin of osteoclasts, the role of BRD9 in osteoclastogenesis and bone diseases remains unresolved. Here, we show Brd9 deficiency in myeloid lineage enhances osteoclast lineage commitment and bone resorption through downregulating interferon-beta (IFN-β) signaling with released constraint on osteoclastogenesis. Notably, we show that BRD9 interacts with transcription factor FOXP1 activating Stat1 transcription and IFN-β signaling thereafter. Besides, function specificity of BRD9 distinguished from BRD4 during osteoclastogenesis has been evaluated. Leveraging advantages of pharmacological modulation of BRD9 and flexible injectable silk fibroin hydrogel, we design a local deliver system for effectively mitigating zoledronate related osteonecrosis of the jaw and alleviating acute bone loss in lipopolysaccharide-induced localized aggressive periodontitis. Overall, these results demonstrate the function of BRD9 in osteoclastogenesis and its therapeutic potential for bone diseases.
科研通智能强力驱动
Strongly Powered by AbleSci AI