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

Abstract

Dentin matrix protein 1 (DMP1) is a key regulator for osteoblast differentiation and mineralization of the bone extracellular matrix (ECM). Osteocalcin (OCN) is one of the most abundantly expressed non-collagenous protein by osteoblasts in bone. In the present study, we generated a mouse model (OCN-DMP1) that overexpresses full-length DMP1 utilizing the 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-days 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, a unique osteogenic gene expression profile for calvaria and femur, representing intramembranous and endochondral bone formation was identified. These data suggest that bone-specific DMP1 overexpression has a profound influence on bone development by impacting osteogenic gene expression. This animal model presented here provides new opportunities for analysis of in vivo roles of DMP1 in bone.

Composition of elastin like polypeptide–collagen composite scaffold influences in vitro osteogenic activity of human adipose derived stem cells

“…This is also in line with a study performed by Gandavarapu et al, who used thiolene chemistry to functionalize poly(ethylene glycol) hydrogels with a pendant peptide moiety and found that stiffer gels with Young’s modulus of 25 kPa had increased ALP activity on day 14 than the softer hydrogels with a modulus of 2 kPa [46]. Furthermore, OCN is the most abundant non-collagenous protein in bone extracellular matrix [47] and its expression is closely related to bone metabolism including bone extracellular matrix mineralization and turnover [48]. Figure 4 demonstrates the results of OCN assay on different composites.…”

Enhanced bone regeneration capability of chitosan sponge coated with TiO2 nanoparticles

“…Dentin Matrix Protein 1 (DMP1) is a bone-specific important marker for osteocyte formation and phosphate metabolism for maintaining mineralization of the bone extracellular matrix. Mutation on DMP1 gene could cause abnormalities in bone development, such as osteomalcia and rickets [47,48]. Whereas, osteocalcin (OCN) plays its role when precursor cells committed to differentiate into mature osteoblasts.…”

The Effects of Stably Tethered BMP-2 on MC3T3-E1 Preosteoblasts Encapsulated in a PEG Hydrogel

“…68 This gene is involved in osteoblast differentiation, and the protein DMP-1 is critical for proper mineralization of bone ECM. 69 Interestingly, our findings suggest that the hydrogel alone (i.e., without BMP-2) exhibits a greater osteocytic phenotype. Contrarily, the presence of BMP-2 in this hydrogel system appears to retain the MC3T3-E1 differentiation closer to an osteoblastic phenotype, ECM.…”