Osteologie 2021; 30(04): 335
DOI: 10.1055/s-0041-1736712
Abstract

Integrin α2β1 influences bone remodeling by regulating osteoblastogenesis via BMP signaling

M Brand
Department of Regenerative Musculoskeletal Medicine, Institute of Musculoskeletal Medicine, University Hospital Münster, Münster, Germany
,
D Kronenberg
Department of Regenerative Musculoskeletal Medicine, Institute of Musculoskeletal Medicine, University Hospital Münster, Münster, Germany
,
J Everding
Department of Trauma, Hand and Reconstructive Surgery, University Hospital Münster, Münster, Germany
,
L Wendler
Department of Trauma, Hand and Reconstructive Surgery, University Hospital Münster, Münster, Germany
,
R Stange
Department of Regenerative Musculoskeletal Medicine, Institute of Musculoskeletal Medicine, University Hospital Münster, Münster, Germany
› Author Affiliations
› Further Information
 
 

Introduction

Integrin α2β1 is classified to the integrin family, a group of heterodimeric transmembrane receptors with important roles in cell adhesion, cell-cell communication, and interplay of cells with the extracellular matrix. Furthermore, it is one of four collagen-binding integrins and the major receptor for collagen type I in bone tissue. Our group showed that the loss of integrin α2β1 facilitate the expression of collagen type I and protects against age-related osteoporosis [1]. In this study, we investigated the impact of integrin α2β1 in bone metabolism and fracture repair with perspective for clinical use.


#

Material and Methods

Using constitutive knockout mouse model [2] we examine the effect of integrin α2β1 on collagen synthesis and mineralization in bone tissue. We applied biochemical assays, like gene expression level, ELISA and immunofluorescence staining, histological techniques, like Alcian blue staining, and µCT scans.


#

Results

Integrin α2β1-deficient mice exhibit an accelerated fracture repair involving enhanced collagen synthesis, faster callus formation and mineralization. Additionally, the BMP signaling, a key factor for osteogenesis and mineralization, shows an earlier onset and enhanced activation during osteoblastic differentiation in vitro. The mineralization develops faster, the BMP-2 expression level and extracellular located protein level is earlier enhanced, and the downstream signaling via activation of SMAD1 is earlier elevated.


#

Conclusion

These results point out that the absence of integrin α2β1 leads to an improved fracture repair by accelerated signaling of pro-osteogenic factor BMP-2. Therefore, we conclude a regulating role of Integrin α2β1 on bone metabolism. This recent insight may facilitate new therapeutic approach for fracture repair and non-unions.


#
#

Conflict of Interest

All named authors declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

  • References

  • 1 Stange et al. Bone 2013; 56(1): 48–54.
  • 2   Holtkotter et al. J Biol Chem 2002; 277(13): 10789–94

Publication History

Article published online:
04 November 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Stange et al. Bone 2013; 56(1): 48–54.
  • 2   Holtkotter et al. J Biol Chem 2002; 277(13): 10789–94