CYP27A1 deficiency promoted osteoclast differentiation

PeerJ

article

Ziqi Fang¹  Guangdong Cheng²  Mengting He³  Yanliang Lin¹ 

[1]Department of Clinical Laboratory, Shandong Provincial Hospital, Shandong University

[2]Department of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University

[3]Department of Critical Care Medicine, Shandong University of Traditional Chinese Medicine

关键词: CYP27A1;    Osteoclasts;    Bone loss;    RNA sequencing;    Expression profile;   

DOI  :  10.7717/peerj.15041

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Background 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. Methods 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. Results 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. Conclusions These results suggested that CYP27A1 was involved in osteoclast differentiation, providing a novel therapeutic target for osteoclast-related diseases.

【 授权许可】

CC BY