Integrin α2β1 affects fracture healing by elevated collagen expression and impaired bone remodeling

Introduction:

The transmembrane receptor integrin α2β1, one out of four collagen-binding integrins, is the major receptor for collagen type I in bone tissue and has important function in the cell-cell communication and cell-matrix interaction. We investigated the effect of integrin α2β1 in bone metabolism and fracture repair and evaluated possibilities for clinical use.

Materials and methods:

Using an integrin α2β1-knockout mouse model we investigated the impact of integrin α2β1 deficiency on fracture repair and collagen synthesis in-vitro and in-vivo by molecular biological and histological techniques, e.g. Western blot analysis, immunofluorescence staining, Alcian blue staining, and by µCT scans.

Results:

Integrin α2β1-deficient mice displayed an increased collagen expression, an accelerated fracture repair by enhanced callus formation and faster bone remodeling. We further observed in fractured femora of α2β1-deficient mice a trend to an elevated phosphoSMAD2 expression and a translocation of phosphoSMAD2 from the cytosol into the nucleus in integrin α2β1-deficient preosteoblasts.

Discussion:

Our results point out that integrin α2β1 affects physiological processes in bone metabolism by regulating signaling pathways with importance for improved fracture healing. To determine the underlying mechanism we will further investigate the impact of integrin α2β1-deficiency on TGF-β and BMP-2 signaling which is closely connected to collagen expression and bone generation by the signaling of the SMAD family. This mechanism might serve as a therapeutic approach to improve the healing process of complex fractures and non-unions.

Key words:

Integrin α2β1, fracture healing, bone metabolism, collagen type I