Response of mesenchymal stem cells to micro-textured surfaces in vitro

OBJECTIVES: Bone metabolism changes and bone regeneration decreases with advancing age in humans, which results in a high risk of implant failure in the elderly. Young adult mice with fibroblast growth factor receptor 3 (FGFR3-/-) deficiency exhibit defects in bone metabolism, similar to those seen in the elderly, which compromise bone regeneration. The objective of our work is to characterize the cellular and molecular responses of FGFR3-/- bone marrow-derived stromal cells (MSC) to micro-textured surfaces, which have been shown to enhance bone regeneration in vivo.

METHODS: MSC harvested from 4 month old FGFR3-/- mice and their wild type littermates were grown in-vitro on smooth or micro-textured titanium discs, to simulate the in-vivo environment of bone regeneration on implants and grafts. Cell proliferation, differentiation, and mineralization were assessed using MTS assay, alkaline phosphatase and Von Kossa staining respectively. Changes in gene expression induced by micro-textured surfaces and FGFR3 deficiency were assessed using RT-PCR and gene expression profiling.

RESULTS: Proliferation of MSC from FGFR3-/- mice was increased compared with wild type mice, but was not affected by surface topography in either genotype. In contrast, micro-textured surfaces enhanced osteogenic differentiation of wild type and FGFR3-/- cells. Gene expression profiling and gene network analysis suggested the potential involvement of egr1, dio2, fibronectin and MMP in the response of MSC to micro-textured surfaces.

CONCLUSION: Micro-textured surfaces enhanced the osteogenic differentiation of MSC harvested from young adult FGFR3-/- mice, which have been characterized with osteopenia and osteomalacia. Several genes have been identified that may contribute to enhanced bone formation in the absence of FGFR3 signaling. These genes represent potential molecular targets to improve osseointegration and bone regeneration in elderly patients receiving oral and orthopedic implants.