Multi-scale analysis of bone chemistry, morphology and mechanics in the oim model of osteogenesis imperfecta

Abstract

Osteogenesis imperfecta is a congenital disease commonly characterized by brittle bones and caused by mutations in the genes encoding Type I collagen, the single most abundant protein produced by the body. The oim model has a natural collagen mutation, converting its heterotrimeric structure (two α1 and one α2 chains) into α1 homotrimers. This mutation in collagen may impact formation of the mineral phase, creating a brittle bone phenotype in this animal. Femurs from male wild type (WT) and homozygous (oim/oim) mice, all at 12 weeks of age, were assessed using assays at multiple length scales with minimal sample processing to ensure a near-physiological state. Atomic force microscopy (AFM) demonstrated detectable differences in the organization of collagen at the nanoscale that may partially contribute to alterations in material and structural behavior obtained through mechanical testing and reference point indentation (RPI). Changes in geometric and chemical structure obtained Multi-scale analyses of this nature offer much in assessing how molecular changes compound to create a degraded, brittle bone phenotype.

Bone structure assessed by HR-pQCT, TBS and DXL in adult patients with different types of osteogenesis imperfecta

“…1 and 2). The relationship between changes in collagen and bone microstructure including trabecular bone volume, trabecular number, and thickness as well as cortical thickness was reported recently in mice models of OI [25,26], but not in humans. Deterioration of the trabecular bone microarchitecture in adults with OI can be partly explained by the lack of origination and secondary thickening of trabeculae during childhood.…”

Exercise prevents β-aminopropionitrile-induced morphological changes to type I collagen in murine bone

“…A similar downward shift in D-spacing distribution was observed in a murine model of osteogenesis imperfecta. 20 In a rat model of type 2 diabetes mellitus, increased non-enyzmatic crosslinking tended to shift the D-spacing distribution up in bone and tendon, suggesting that greater overall crosslinking (whether enzymatic or nonenzymatic) is associated with increased D-spacing distributions. 21,22 The downward shift reported here was rectified to PBS control levels when exercise was introduced in BAPN mice ( Figure 1c).…”

Contributions of Raman spectroscopy to the understanding of bone strength

“…Hardness and indentation modulus appear to be independent of mineral/matrix and carbonate/phosphate ratios until substantial amounts of mineral are laid down, although the authors fit their entire data set to straight lines. 47 There are a few studies of the correlation between biomechanical parameters and Raman spectroscopic composition parameters in mouse models of disorders, including osteogenesis imperfect (OI) [48][49][50][51] and osteoporosis, 52 as well as on the effects of knocking out matrix proteinase, 53 transcription factor 54 and noncollagenous proteins. [55][56][57][58][59][60][61][62] These are discussed in the following sections.…”