Age-related bone deterioration is diminished by disrupted collagen sensing in integrin α2β1 deficient mice

Bone. 2013 Sep;56(1):48-54. doi: 10.1016/j.bone.2013.05.003. Epub 2013 May 13.

Abstract

Collagen binding integrins are of essential importance in the crosstalk between cells and the extracellular matrix. Integrin α2β1 is a major receptor for collagen I, the most abundant protein in bone. In this study we show for the first time that integrin α2 deficiency is linked to collagen type I expression in bone. Investigating the femurs of wild type and integrin α2β1 deficient mice, we found that loss of integrin α2 results in altered bone properties. Histomorphometric analysis of integrin α2 long bones displayed more trabecular network compared to wild type bones. During age related bone loss the integrin α2β1 deficient bones retain trabecular structure even at old age. These findings were supported by functional, biomechanical testing, wherein the bones of integrin α2β1 deficient mice do not undergo age-related alteration of biomechanical properties. These results might be explained by the increased presence of collagen in integrin α2β1 deficient bone. Collagen type I could be detected in higher quantities in the integrin α2β1 deficient bones, forming abnormal, amorphous fibrils. This was linked to higher expression levels of collagen type I and other bone formation related proteins as alkaline phosphatase of integrin α2β1 deficient osteoblasts. Osteoclasts of integrin α2β1 deficient mice did not show any differences. Consequently these results indicate that the absence of integrin α2β1 alleviates the effects of age related bone degradation through over-expression of collagen type I and demonstrate a molecular mechanism how collagen binding integrins might directly impact bone aging.

Keywords: Aging; Bone metabolism; Collagen type I; Collagen-binding integrins; Osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics
  • Aging / pathology*
  • Animals
  • Biomarkers / metabolism
  • Biomechanical Phenomena
  • Bone Resorption / genetics
  • Bone Resorption / pathology*
  • Calcification, Physiologic / genetics
  • Cell Count
  • Cell Differentiation / genetics
  • Collagen Type I / genetics
  • Collagen Type I / metabolism*
  • Dissection
  • Female
  • Femur / pathology
  • Femur / physiopathology
  • Femur / ultrastructure
  • Fibrillar Collagens / genetics
  • Fibrillar Collagens / metabolism
  • Fibrillar Collagens / ultrastructure
  • Gene Expression Regulation
  • Integrin alpha2beta1 / deficiency*
  • Integrin alpha2beta1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Biomarkers
  • Collagen Type I
  • Fibrillar Collagens
  • Integrin alpha2beta1
  • RNA, Messenger
  • collagen type I, alpha 1 chain