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Early fracture healing is delayed in the Col1a2+/G610C osteogenesis imperfecta murine model

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.
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https://www.hal.inserm.fr/inserm-01859541
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Submitted on : Wednesday, August 22, 2018 - 11:35:14 AM
Last modification on : Tuesday, September 28, 2021 - 4:14:06 PM
Long-term archiving on: : Friday, November 23, 2018 - 2:48:35 PM

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Besio Roberta, Sylvia Maruelli, Séverine Battaglia, Laura Leoni, Simona Villani, et al.. Early fracture healing is delayed in the Col1a2+/G610C osteogenesis imperfecta murine model . Calcified Tissue International, Springer Verlag, 2018, Epub ahead of print. ⟨10.1007/s00223-018-0461-x⟩. ⟨inserm-01859541⟩

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