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.

软骨细胞的增生和肥大在软骨内骨化中起重​​要作用，软骨内骨化在骨骼发育过程中受到严格调节。但是，调节机制在很大程度上仍然未知。在这里，我们显示DDB1（受损的DNA结合蛋白1）在生长板的发育中具有关键功能。使用软骨细胞特异性DDB1基因敲除小鼠，我们发现由于异常骨骼发育，软骨细胞中DDB1缺失导致侏儒症。胫骨中生长板的结构在P21处变得混乱，而在股骨处则变得混乱。但是在P70时，股骨的变化比胫骨更严重。在P7和P21处，胫骨和股骨的软骨细胞增殖和分化减弱且不同步。此外，DDB1缺乏诱导原代软骨细胞中p27上调和随后的细胞周期停滞。因此，我们的数据显示DDB1通过控制软骨细胞的增殖和分化对于骨骼发育至关重要。