Bone-specific overexpression of DMP1 influences osteogenic gene expression during endochondral and intramembranous ossification

Abstract

Dentin matrix protein 1 (DMP1) is a key regulator of biomineralization within the extracellular matrix (ECM) of bone and plays a role in regulating osteogenic gene expression. Osteocalcin (OCN) is one of the most abundantly expressed non-collagenous proteins by osteoblasts. In the present study, we generated a mouse model (OC-DMP1) that overexpresses full-length DMP1 utilizing the mouse OCN promoter. Expression of genes encoding osteogenic transcription factors and ECM proteins during early post-natal development in male OC-DMP1 and wild type (WT) mice was evaluated in femurs and calvaria. Bones were dissected from n = 4 animals at 15, 30, 60 and 90-d of age. Total RNA was isolated, reverse transcribed, and real-time PCR analysis was performed. Results confirmed a difference (p < 0.05) in osteogenic gene expression between OC-DMP1 and WT mice at the specified time points. Additionally, distinctive osteogenic gene expression profiles for calvaria and femur, representing intramembranous and endochondral bone formation, were identified. These data suggest that bone-specific DMP1 overexpression changes the pattern in osteogenic gene expression pattern thereby influencing bone development. This animal model presented here provides new opportunities for analysis of in vivo roles of DMP1 in bone.