Osteogenic gene array of osteoblasts cultured on a novel osteoinductive biphasic calcium phosphate bone grafting material.

Abstract

Recently, novel biphasic calcium phosphate (BCP) scaffolds have emerged as a new class of bone grafts with osteoinductive potential demonstrating the ability to form ectopic bone in extra-skeletal sites. The aim of the present study was to perform an osteogenic gene array to target possible genes responsible for eliciting the changes in cell expression responsible for inducing osteoblast differentiation. Human MG63 osteoblast-like cells were seeded for 24h on tissue culture plastic or osteoinductive BCP particles and analyzed for upregulated genes using an osteogenesis super-array. Osteoblast-related genes including those transcribed during bone mineralization, bone metabolism, cell growth and differentiation, as well as gene products representing extracellular matrix molecules, transcription factors, and cell adhesion molecules were investigated. An upregulation of genes transcribing biglycan (1.7-fold), bone morphogenetic proteins 1, 2, 4, 6, and 7 (1.5-2.1-fold), various collagen isoforms including 1a1, 1a2, 2a1, and 5a1 (1.73-2.72-fold), colony stimulating factor 2 (2.59-fold), fibroblast growth factor receptor 2 (1.79-fold), fibronectin (2.56-fold), integrin alpha 1, 2, and 3 (1.82-2.24-fold), SOX9 (2.75-fold), transforming growth factor beta receptor 2 (1.72-fold), vitamin D (1.89-fold), and vascular endothelial growth factor A and B (2.00, 1.75-fold) were all significantly (p<0.05) increased on BCP particles when compared to control tissue culture plastic. In summary, a number of activated genes were involved in bone formation following osteoblast attachment to BCP particles. The involvement of key chondrogenic genes hints that bone grafts capable of spontaneously inducing ectopic bone formation may implicate endochondral ossification. Further investigations in the triggered pathways involved in the process of ectopic bone formation are necessary to understand the key inductive properties of these novel osteoinductive BCP particles. Novel osteoinductive BCP particles demonstrate a wide range of significant increases over several key molecules implicated in osteogenesis that may be implicated in their ability to form ectopic bone formation.