Cortical and trabecular morphology is altered in the limb bones of mice artificially selected for faster skeletal growth

Farooq, Saira; Leussink, Shannon; Sparrow, Leah M.; Marchini, Marta; Britz, Hayley M.; Manske, Sarah L.; Rolian, Campbell

doi:10.1038/s41598-017-10317-x

Cited by 15 publications

(23 citation statements)

References 63 publications

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“…Specifically, the tibia's cross-sectional area and polar section modulus in LS1 did not change appreciably, which led us to predict that it is significantly less resistant to bending moments. In a related study (Farooq et al 2017), we found that tibia trabecular microarchitecture had been substantially altered in parallel with increases in tibia length in both Longshanks lines, potentially altering its ability to withstand compressive loads. In the present study, we investigated whether the altered shape of the Longshanks tibia has impacted its strength and elastic properties.…”

Section: Introductionmentioning

confidence: 66%

Selection for longer limbs in mice increases bone stiffness and brittleness, but does not alter bending strength

Cosman

Britz

Rolian

2019

Journal of Experimental Biology

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The ability of a bone to withstand loads depends on its structural and material properties. These tend to differ among species with different modes of locomotion, reflecting their unique loading patterns. The evolution of derived limb morphologies, such as the long limbs associated with jumping, may compromise overall bone strength. We evaluated bone mechanical properties in the Longshanks mouse, which was selectively bred for increased tibia length relative to body mass. We combined analyses of 3D shape and cross-sectional geometry of the tibia, with mechanical testing and bone composition assays, to compare bone strength, elastic properties and mineral composition in Longshanks mice and randomly bred controls. Our data show that, despite being more slender, cortical geometry and predicted bending strength of the Longshanks tibia were similar to controls. In whole bone bending tests, measures of bone bending strength were similar across groups; however, Longshanks tibiae were significantly more rigid, more brittle, and required less than half the energy to fracture. Tissue-level elastic properties were also altered in Longshanks mice, but the bones did not differ from the control in water content, ash content or density. These results indicate that while Longshanks bones are as strong as control tibiae, selection for increased tibia length has altered its elastic properties, possibly through changes in organic bony matrix composition. We conclude that selection for certain limb morphologies, and/or selection for rapid skeletal growth, can lead to tissue-level changes that can increase the risk of skeletal fracture, which in turn may favor the correlated evolution of compensatory mechanisms to mitigate increased fracture risk, such as delayed skeletal maturity.

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Section: Introductionmentioning

confidence: 66%

Selection for longer limbs in mice increases bone stiffness and brittleness, but does not alter bending strength

Cosman

Britz

Rolian

2019

Journal of Experimental Biology

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“…Some of these variables have been demonstrated to follow non‐linear patterns of change over the lifespan. Mice selectively bred for accelerated skeletal growth had significantly less BV/TV, Tb.N, and Tb.Th than controls (Farooq et al ), indicating that some aspects of trabecular bone quality could be compromised during periods of rapid postnatal growth. Intriguingly, BV/TV and Tb.N decrease between 6 and 12 months of age in the proximal human femur, with the lowest values for these parameters occurring in individuals just under 1 year of age.…”

Section: Discussionmentioning

confidence: 99%

Ontogenetic changes to bone microstructure in an archaeologically derived sample of human ribs

2019

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There is considerable variation in the gross morphology and tissue properties among the bones of human infants, children, adolescents, and adults. Using 18 known‐age individuals (nfemale = 8, nmale = 9, nunknown = 1; birth to 21 years old), from a well‐documented cemetery collection, Spitalfields Christ Church, London, UK, this study explores growth‐related changes in cortical and trabecular bone microstructure. Micro‐CT scans of mid‐shaft middle thoracic ribs are used for quantitative analysis. Results are then compared to previously quantified conventional histomorphometry of the same sample. Total area (Tt.Ar), cortical area (Ct.Ar), cortical thickness (Ct.Th), and the major (Maj.Dm) and minor (Min.Dm) diameters of the rib demonstrate positive correlations with age. Pore density (Po.Dn) increases, but age‐related changes to cortical porosity (Ct.Po) appear to be non‐linear. Trabecular thickness (Tb.th) and trabecular separation (Tb.Sp) increase with age, whereas trabecular bone pattern factor (Tb.Pf), structural model index (SMI), and connectivity density (Conn.D) decrease with age. Sex‐based differences were not identified for any of the variables included in this study. Some samples display clear evidence of diagenetic alteration without corresponding changes in radiopacity, which compromises the reliability of bone mineral density (BMD) data in the study of past populations. Cortical porosity data are not correlated with two‐dimensional measures of osteon population density (OPD). This suggests that unfilled resorption spaces contribute more significantly to cortical porosity than do the Haversian canals of secondary osteons. Continued research using complementary imaging techniques and a wide array of histological variables will increase our understanding of age‐ and sex‐specific ontogenetic patterns within and among human populations.

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“…Breeders were selected at eight weeks, at which point longitudinal tibia growth is over 97% complete (Farooq et al. , see further). Longshanks mice at generation F14 showed an increase of 9–13% in tibia length relative to body mass.…”

Section: Methodsmentioning

confidence: 99%

Artificial selection sheds light on developmental mechanisms of limb elongation

Marchini

Rolian

2018

Evolution

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Species diversity in limb lengths and proportions is thought to have evolved adaptively in the context of locomotor and habitat specialization, but the heritable cellular processes that drove this evolution within species are poorly understood. In this study, we take a novel "micro-evo-devo" approach, using artificial selection on relative limb length to amplify phenotypic variation in a population of mice, known as Longshanks, to examine the cellular mechanisms of postnatal limb development that contribute to intraspecific limb length variation. Cross-sectional growth data indicate that differences in bone length between Longshanks and random-bred controls are not due to prolonged growth, but to accelerated growth rates. Histomorphometric and cell proliferation assays on proximal tibial growth plates show that Longshanks' increased limb bone length is associated with an increased number of proliferative chondrocytes. In contrast, we find no differences in other growth plate cellular features known to underlie interspecific differences in limb bone size and shape, such as the rates of chondrocyte proliferation or the size and number of hypertrophic cells in the growth plate. These data suggest that small differences among individuals in the number of proliferating chondrocytes are a potentially important determinant of selectable intraspecific variation in individual limb bone lengths, independent of body size.

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Cortical and trabecular morphology is altered in the limb bones of mice artificially selected for faster skeletal growth

Cited by 15 publications

References 63 publications

Selection for longer limbs in mice increases bone stiffness and brittleness, but does not alter bending strength

Selection for longer limbs in mice increases bone stiffness and brittleness, but does not alter bending strength

Ontogenetic changes to bone microstructure in an archaeologically derived sample of human ribs

Artificial selection sheds light on developmental mechanisms of limb elongation

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