Previous studies have demonstrated that osteogenic protein-1 (OP-1), a member of the bone morphogenetic protein (BMP) subfamily of the TGF-beta superfamily, stimulates aggrecan synthesis. To investigate transcriptional regulation of the aggrecan gene by OP-1, we constructed a clone containing a I kb region of the 5'-upstream sequence of the mouse aggrecan-gene fused to the promoter-less luciferase reporter gene in pGL2-Basic vector. A series of promoter deletion constructs were also generated. Studies of the promoter activity of these DNA constructs in transient-transfected cells revealed that deletion of a 33 bp region rendered the promoter unresponsive to OP-1, BMP-6, and CDMP-I without affecting BMP-2 and TGF-beta1 responsiveness. Thus, the expression of the mouse aggrecan gene in response to BMPs appears to be the result of a unique combination of different cis-acting elements. (C) 2004 Elsevier Inc. All rights reserved.