Format

Send to

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

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

Author information

1
Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Via Taramelli 3B, 27100, Pavia, Italy.
2
INSERM, UMR 1238, PHY-OS, Bone sarcomas and remodeling of calcified tissues, Faculty of Medicine, University of Nantes, Nantes, France.
3
Department of Public Health and Experimental and Forensic Medicine, Unit of Biostatistics and Clinical Epidemiology, University of Pavia, Pavia, Italy.
4
Department of Molecular Medicine, Biochemistry Unit, University of Pavia, Via Taramelli 3B, 27100, Pavia, Italy. aforlino@unipv.it.

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

PMID:
30076439
DOI:
10.1007/s00223-018-0461-x

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center