Early Fracture Healing is Delayed in the Col1a2 +/G610C Osteogenesis Imperfecta Murine Model

Calcif Tissue Int. 2018 Dec;103(6):653-662. doi: 10.1007/s00223-018-0461-x. Epub 2018 Aug 3.

Abstract

Osteogenesis imperfecta (OI) is a rare heritable skeletal dysplasia mainly caused by type I collagen abnormalities and characterized by bone fragility and susceptibility to fracture. Over 85% of the patients carry dominant mutations in the genes encoding for the collagen type I α1 and α2 chains. Failure of bone union and/or presence of hyperplastic callus formation after fracture were described in OI patients. Here we used the Col1a2+/G610C mouse, carrying in heterozygosis the α2(I)-G610C substitution, to investigate the healing process of an OI bone. Tibiae of 2-month-old Col1a2+/G610C and wild-type littermates were fractured and the healing process was followed at 2, 3, and 5 weeks after injury from fibrous cartilaginous tissue formation to its bone replacement by radiography, micro-computed tomography (µCT), histological and biochemical approaches. In presence of similar fracture types, in Col1a2+/G610C mice an impairment in the early phase of bone repair was detected compared to wild-type littermates. Smaller callus area, callus bone surface, and bone volume associated to higher percentage of cartilage and lower percentage of bone were evident in Col1a2+/G610C at 2 weeks post fracture (wpf) and no change by 3 wpf. Furthermore, the biochemical analysis of collagen extracted from callus 2 wpf revealed in mutants an increased amount of type II collagen, typical of cartilage, with respect to type I, characteristic of bone. This is the first report of a delay in OI bone fracture repair at the modeling phase.

Keywords: Callus; Collagen; Fracture repair; Osteogenesis imperfecta; µCT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen Type I / genetics*
  • Disease Models, Animal
  • Fracture Healing / genetics*
  • Mice
  • Mutation
  • Osteogenesis Imperfecta / genetics*
  • Osteogenesis Imperfecta / pathology*

Substances

  • Col1a2 protein, mouse
  • Collagen Type I