DDB1 promotes the proliferation and hypertrophy of chondrocytes during mouse skeleton development

• Published in: Developmental biology Vol. 465; no. 2; pp. 100 - 107
• Main Authors: Zhao, Lianzheng, Wang, Xiaodan, Pomlok, Kumpanat, Liao, Hongwei, Yang, Guan, Yang, Xiao, Chen, Ye-Guang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.09.2020
• Subjects: Animals; Bone; bone formation; Cell cycle; Cell Cycle Checkpoints; Chondrocyte; chondrocytes; Chondrocytes - metabolism; Chondrocytes - pathology; DDB1; DNA-binding proteins; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; dwarfing; femur; Femur - growth & development; Femur - pathology; Growth plate; Growth Plate - metabolism; Growth Plate - pathology; Hypertrophy; knockout mutants; Mice; Mice, Knockout; Musculoskeletal Development; p27; skeleton; tibia; Tibia - growth & development; Tibia - pathology; DDB1; Growth plate; Bone; Chondrocyte; p27; Cell cycle
• ISSN: 0012-1606; 1095-564X; 1095-564X
• DOI: 10.1016/j.ydbio.2020.05.011

The proliferation and hypertrophy of chondrocytes play important roles in endochondral ossification, which is tightly regulated during skeleton development. However, the regulation mechanism remains largely unknown. Here we show that DDB1 (Damaged DNA Binding Protein 1) has a critical function in the development of growth plates. Using chondrocyte-specific DDB1 knockout mice, we found that DDB1 deletion in chondrocytes results in dwarfism due to the aberrant skeleton development. The structure of growth plate in tibia becomes disordered at P21, not in femur. But at P70, the changes are severer in femur than tibia. Chondrocyte proliferation and differentiation are attenuated and asynchronous in both tibia and femur at P7 and P21. Furthermore, DDB1 deficiency induces p27 upregulation and subsequent cell cycle arrest in primary chondrocytes. Therefore, our data reveal that DDB1 is essential for the skeleton development by controlling chondrocyte proliferation and differentiation. [Display omitted] •Chondrocyte-specific DDB1 knockout mice exhibit dwarfism and dyschondroplasia.•The mutant growth plates in tibia and femur are structurally disordered with abnormal proliferation and differentiation.•DDB1 controls cartilage development via p27-mediated cell cycle regulation.