NELL-1 binds to APR3 affecting human osteoblast proliferation and differentiation

Zhejiang California International NanoSystems Institute, Zhejiang University, Hangzhou, PR China.
FEBS letters (Impact Factor: 3.34). 06/2011; 585(15):2410-8. DOI: 10.1016/j.febslet.2011.06.024
Source: PubMed

ABSTRACT 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.

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