CYP27A1 deficiency promoted osteoclast differentiation.
CYP27A1 deficiency promoted osteoclast differentiation.
复制标题
细胞色素P27A1缺乏促进破骨细胞分化。
作者：
Fang Z;Cheng G;He M;Lin Y
破骨细胞分化水平升高可导致骨稳态失衡，从而导致骨丢失和骨质疏松等骨疾病。破骨细胞的形成有多种途径和分子参与，但CYP 27 A1在破骨细胞分化中的作用尚未被研究。使用CRISPR-Cas9系统构建CYP 27 A1缺陷型小鼠。TRAP染色检测破骨细胞分化。使用RNA-seq分析鉴定差异表达基因（DEG），并通过qRT-PCR和Western印迹进行确认。结果表明，CYP 27 A1基因敲除（KO）促进破骨细胞分化和骨丢失。转录组学分析显示，CYP 27 A1 KO导致多个基因的差异表达，包括ELANE、LY 6C 2、S100 A9、GM 20708、BGN、CYP 27 A1和COL 1A 2，qRT-PCR和Western blot证实了这一点。富集分析表明，这些差异基因与成骨相关信号通路相关，如PPAR信号通路、IL-17信号通路和PI 3 K/AKT信号通路，qRT-PCR和Western blot证实了这一点。这些结果表明，CYP 27 A1参与破骨细胞的分化，为破骨细胞相关疾病提供了一个新的治疗靶点。
The elevating osteoclast differentiation can lead to an imbalance in bone homeostasis, which was responsible for bone loss and bone diseases, such as osteoporosis. Multiple pathways and molecules have been involved in osteoclast formation, but the role of CYP27A1 in osteoclast differentiation has never been explored. CYP27A1 deficient mice were constructed using CRISPR-Cas9 system. Osteoclast differentiation was detected by TRAP staining. Differentially expressed genes (DEGs) were identified using RNA-seq analysis and were confirmed by qRT-PCR and Western blot. The results showed that CYP27A1 knockout (KO) promoted osteoclast differentiation and bone loss. The transcriptomic analysis revealed that CYP27A1 KO led to differential expression of multiple genes, including ELANE, LY6C2, S100A9, GM20708, BGN, SPARC, and COL1A2, which were confirmed by qRT-PCR and Western blot. Enrichment analysis indicated that these differential genes were significantly associated with osteogenesis-related pathways, such as PPAR signaling, IL-17 signaling, and PI3K/AKT signaling, which were confirmed by qRT-PCR and Western blot. These results suggested that CYP27A1 was involved in osteoclast differentiation, providing a novel therapeutic target for osteoclast-related diseases.
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影响因子：
82.9
作者：
Wan, Yihong;Chong, Ling-Wa;Evans, Ronald M.
通讯作者：
Evans, Ronald M.
影响因子：
6
作者：
Rochette L;Dogon G;Rigal E;Zeller M;Cottin Y;Vergely C
通讯作者：
Vergely C
影响因子：
9.8
作者：
BERGINER, VM;SHANY, S;GAZIT, D
通讯作者：
GAZIT, D
影响因子：
4.6
作者：
Kram V;Kilts TM;Bhattacharyya N;Li L;Young MF
通讯作者：
Young MF
镉暴露通过 P2X7/PI3K/AKT 介导的成骨细胞和破骨细胞分化引发鸭骨质疏松
影响因子：
9.8
作者：
Ma, Yonggang;Ran, Di;Liu, Zongping
通讯作者：
Liu, Zongping