ECTS Abstracts (2015) 1 P399

Altered Osteocyte Lacunae Characteristics in Brtl/+ Mice: a Model for Osteogenesis Imperfecta Type IV

Stéphane Blouin1, Nadja Fratzl-Zelman1, Wayne A Cabral2, Klaus Klaushofer1, Paul Roschger1 & Joan C Marini2

1Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling 1st Medical Department, Hanusch Hospital, Vienna, Austria; 2Bone and Extracellular Matrix Branch, NICHD, NIH, Bethesda, MD, USA.

Osteogenesis imperfecta (OI) is a genetic disorder caused by mutations in genes encoding type I collagen or collagen-interacting proteins. The Brtl/+ mouse is a model for dominant type IV OI, with a Gly349Cys substitution in one COL1A1 allele resulting in long bone fragility. Bone material quality is known to be altered in OI. However little is known about the impact of OI on osteocyte lacunae. We investigated osteocyte lacunar density, size and shape using 2D-image analyses of sectioned Brtl/+ cortical bone. Transverse (wild-type n=6; Brtl/+n=6) and longitudinal (wild-type n=10; Brtl/+n=8) femoral midshaft sections from 2-month old mice were acquired by quantitative Backscattered Electron Imaging. The image grey-levels were thresholded at a value corresponding to 5.2 weight% calcium content. We obtained binary images of sectioned osteocyte lacunae areas (OL) in the range of 1.55 μm2 to 80 μm2. We measured the OL density, OL-related porosity and frequency distribution of OL area, perimeter and aspect ratio between major and minor axes (AR). Neither OL density nor porosity were significantly different between wild-type and Brtl/+ in transverse and longitudinal sections. Independent of section orientation, the size distribution of lacunae showed decreased heterogeneity in Brtl/+, with higher numbers of intermediate OL and lower numbers of small and large OL per surface in Brtl/+ vs WT. For instance, in the frequency distribution of OL area in transverse sections, Brtl/+ vs wild-type -18% in the 1.55 to 10 μm2 range, +23% in the 10 to 20 μm2 range and -32% in the 60 to 70 μm2 range. Additionally, the OL shape in Brtl/+ were significantly more elongated, consistent with lacunar size distribution and with detection of more lacunae in transverse than longitudinal sections. These data suggest that osteocyte lacunar formation is altered in OI, which could be secondary to either osteocyte dysfunction or mutant collagen structure.

Disclosure: The authors declared no competing interests.

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