Here we demonstrated that overexpression of Osterix can suppress NELL-1 expression at the transcriptional level in multiple human osteoblast-like and non-osteoblastic cell lines, and verified that this inhibitory effect on NELL-1 expression with and without Runx2 induction involves Osterix direct binding of Sp1 sites in the NELL-1 promoter in a human osteosarcoma cell line, Saos2. Here, SP7 is linked to osteosarcoma.