Osteoblasts respond to hydroxyapatite surfaces with immediate changes in gene expression

Abstract

Bone mineral contains hydroxyapatite (HA). This is the surface that mature osteoblasts and osteocytes interact with. Synthetic HA is widely used in orthopedic surgeries as an implant or implant coating. The bone-like HA surfaces increase implant union and bone formation; however, the mechanisms accounting for this effect on osteoblasts are not known. In this study, we compared gene expression profiles of osteoblasts responding to HA or plastic surfaces for 24 h. Expression profiles were also compared between HA discs processed with gravity-sieved compared with combined gravity and air-jet-sieved HA powders. The latter, composed of smaller HA particles, exhibits an increase in grain boundary surface area. Discs made with either HA powder similarly up-regulated osteoblast expression of 10 genes (including proliferin 3, Glvr-1, DMP-1, and tenascin C) and down-regulated 15 genes (such as osteoglycin) by more than 2-fold compared with plastic surfaces. The overall changes are indicative of an immediate (24-h) response to the HA surface and a trend toward osteoblast differentiation. In addition, subsets of modulated genes exist that are unique to each HA subtype. Taken together, we identified HA responsive genes evident within 24 h of surface contact, indicating a critical role for extracellular mineral surfaces in the regulation of osteoblast gene expression and phenotype.

Initial responses of human osteoblasts to sol–gel modified titanium with hydroxyapatite and titania composition

“…Both OP and COL I gene expression were shown to enhance with increased HA coating composition, consistent with literature suggesting that there may be a group of HA-responsive genes in osteoblasts that are evident within 24 h of first surface contact [21]. Only BSP exhibited greatest gene expression at the HA+10%TiO2 optimal surface for cell proliferation.…”

The development of non-viral gene-activated matrices for bone regeneration using polyethyleneimine (PEI) and collagen-based scaffolds

“…From a bone repair perspective, the addition of a nHa phase to the matrix serves to theoretically increase the osteogenic potential of the scaffold. Hydroxyapatite is an osteoconductive material that encourages osteoblast differentiation [54] and when hydroxyapatite is combined with collagen in a tissue engineering scaffold, it leads to increased matrix deposition by seeded cells [55]. Its use in scaffolds for bone tissue engineering therefore has obvious advantages, especially if further enhanced by combining nHa scaffolds with gene therapy.…”

Calcium orthophosphate-based biocomposites and hybrid biomaterials

“…Collagen alone is not effective as an osteoinductive material, but it becomes osteoconductive in combination with calcium orthophosphates [585]. Both collagen type I and HA were found to enhance osteoblast differentiation [586] but combined together, they were shown to accelerate osteogenesis. However, this tendency is not so straightforward: the data are available that implanted HA/ collagen biocomposites enhanced regeneration of calvaria bone defects in young rats but postponed the regeneration of calvaria bone in aged rats [587].…”