ABSTRACT
BACKGROUND: Distraction osteogenesis is a valuable clinical tool; however the molecular mechanisms governing successful distraction remain unknown. We have used a uniaxial in vitro strain device to simulate the uniaxial mechanical environment of the interfragmentary distraction gap. MATERIALS AND METHODS: Using the Flexcell system, normal human osteoblasts were subjected to different levels of cyclical uniaxial mechanical strain. Cellular morphology, proliferation, migration, and the expression of angiogenic (vascular endothelial growth factor [VEGF] and fibroblast growth factor-2 [FGF-2]) and osteogenic (osteonectin, osteopontin, and osteocalcin) proteins and extracellular matrix molecules (collagen IalphaII) were analyzed in response to uniaxial cyclic strain. RESULTS: Osteoblasts exposed to strain assumed a fusiform spindle-shaped morphology aligning parallel to the axis of uniaxial strain and osteoblasts exposed to strain or conditioned media had a 3-fold increase in proliferation. Osteoblast migration was maximal (5-fold) in response to 9% strain. Angiogenic cytokine, VEGF, and FGF-2, increased 32-fold and 2.6-fold (P < 0.05), respectively. Osteoblasts expressed greater amounts of osteonectin, osteopontin, and osteocalcin (2.1-fold, 1.8-fold, 1.5-fold respectively, P < 0.01) at lower levels of strain (3%). Bone morphogenic protein-2 production increased maximally at 9% strain (1.6-fold, P < 0.01). Collagen I expression increased 13-, 66-, and 153-fold in response to 3, 6, and 9% strain, respectively. CONCLUSIONS: Uniaxial cyclic strain using the Flexcell device under appropriate strain parameters provides a novel in vitro model that induces osteoblast cellular and molecular expression patterns that simulate patterns observed in the in vivo distraction gap.
