NELL-1 binds to APR3 affecting human osteoblast proliferation and differentiation
- FEBS Lett. 2011 Aug 4;585(15):2410-8. doi: 10.1016/j.febslet.2011.06.024.
- 1. Zhejiang California International NanoSystems Institute, Zhejiang University, Hangzhou, PR China.
Nel-like protein 1 (NELL-1) is an osteoinductive molecule associated with premature calvarial suture closure. Here we identified Apoptosis related protein 3 (APR3), a membrane protein known as a proliferation suppressor, as a binding protein of NELL-1 by biopanning. NELL-1 and APR3 colocalized on the nuclear envelope of human osteoblasts. NELL-1 significantly inhibited proliferation of osteoblasts co-transfected with APR3 through further down-regulation of Cyclin D1. The co-expression of NELL-1 and APR3 enhanced Ocn and Bsp expression and mineralization. RNAi of APR3 significantly reduced the differentiation effect of NELL-1. These findings suggest that the effects of NELL-1 on osteoblastic differentiation and proliferation are partly through binding to APR3.