scholarly journals Insulin Receptor Deletion in S100a4-lineage cells accelerates age-related bone loss

2018 ◽  
Author(s):  
Valentina Studentsova ◽  
Emma Knapp ◽  
Alayna E. Loiselle
Keyword(s):  
Insulin Receptor ◽  
Volume Fraction ◽  
Bone Cells ◽  
Torsional Rigidity ◽  
Bone Volume ◽  
Type I ◽  
Bone Homeostasis ◽  
Skeletal Health ◽  
Bone Volume Fraction ◽  
Age Related

AbstractType I and Type II Diabetes dramatically impair skeletal health. Altered Insulin Receptor (IR) signaling is a common feature of both diseases, and insulin has potent bone anabolic functions. Several previous studies have demonstrated that loss of IR in bone cells results in disrupted bone homeostasis during early post-natal growth. Here we have deleted IR in S100a4-lineage cells (IRcKOS100a4) and assessed the effects on bone homeostasis at both young (15 weeks) and older adult (48 weeks) mice. S100a4-cre has previously been shown to target the perichondrium during bone development, and here we show that S100a4 is expressed by adult trabecular and cortical bone cells, and that S100a4-Cre effectively targets adult bone, resulting in efficient deletion of IR. Deletion of IR in S100a4-lineage cells does effect initial bone acquisition or homeostasis with no changes in cortical, trabecular or mechanical properties at 15-weeks of age, relative to wild type (WT) littermates. However, by 48-weeks of age, IRcKOS100a4 mice display substantial declines in trabecular bone volume, bone volume fraction and torsional rigidity, relative to age-matched WT controls. This work establishes the utility of using S100a4-cre to target bone and demonstrates that IR in S100a4-lineage cells is required for maintenance of bone homeostasis in adult mice.

Estimation of an early meaningful time point of bone parameter changes in application to an osteoporotic rat model with in vivo microcomputed tomography measurements

2012 ◽  
Vol 46 (3) ◽  
pp. 237-244 ◽  
Author(s):  
Annekathrin Martina Keiler ◽  
Oliver Zierau ◽  
Günter Vollmer ◽  
Dieter Scharnweber ◽  
Ricardo Bernhardt
Keyword(s):  
Bone Turnover ◽  
Volume Fraction ◽  
Expression Profiles ◽  
Lumbar Vertebrae ◽  
Microcomputed Tomography ◽  
Bone Volume ◽  
Marker Genes ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Bone Volume Fraction

The commonly used preclinical animal model of postmenopausal osteoporosis is the mature ovariectomized rat, whereby cessation of ovarian oestrogen production consequently results in bone volume reduction. The study aim was to precisely define the time course of structural changes resulting from ovariectomy and thereby reduce the time animals have to be treated to judge the effects of osteoporosis treatment. For this purpose, we assessed architectural changes by microcomputed tomography ( μCT) during 10 weeks following ovariectomy or sham surgery at two-week intervals. Moreover, the trabecular microarchitecture of the lumbar vertebrae was assessed after necropsy. Besides this, serum biomarkers of bone turnover were determined. These data were in a new approach additionally correlated to femur mRNA expression profiles. We selected the osteoblast marker genes osteocalcin and type I collagen as well as the two osteoclast marker genes cathepsin k and tartrate-resistant acid phosphatase 5. The gene expression analysis suggested an activation of osteoblasts as well as octeoclasts. The significantly induced serum levels of osteocalcin and collagen degradation fragments also revealed this higher rate of bone turnover. Our results indicate that as soon as four weeks after ovariectomy the bone volume fraction exhibited a decline of 30% and 50% of the connectivity density. In addition, significant decreases of trabecular number and thickness as well as of the bone volume fraction were only observed in vertebrae of ovariectomized animals. Interestingly, changes of trabecular morphology were also found in the sham animals as a consequence of senescence.

scholarly journals Bone health in spacefaring rodents and primates: systematic review and meta-analysis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jingyan Fu ◽  
Matthew Goldsmith ◽  
Sequoia D. Crooks ◽  
Sean F. Condon ◽  
Martin Morris ◽  
...  
Keyword(s):  
Bone Formation ◽  
Trabecular Bone ◽  
Bone Health ◽  
Volume Fraction ◽  
Meta Analysis ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
Bone Volume Fraction ◽  
Percentage Difference ◽  
Induced Changes

AbstractAnimals in space exploration studies serve both as a model for human physiology and as a means to understand the physiological effects of microgravity. To quantify the microgravity-induced changes to bone health in animals, we systematically searched Medline, Embase, Web of Science, BIOSIS, and NASA Technical reports. We selected 40 papers focusing on the bone health of 95 rats, 61 mice, and 9 rhesus monkeys from 22 space missions. The percentage difference from ground control in rodents was –24.1% [Confidence interval: −43.4, −4.9] for trabecular bone volume fraction and –5.9% [−8.0, −3.8] for the cortical area. In primates, trabecular bone volume fraction was lower by –25.2% [−35.6, −14.7] in spaceflight animals compared to GC. Bone formation indices in rodent trabecular and cortical bone were significantly lower in microgravity. In contrast, osteoclast numbers were not affected in rats and were variably affected in mice. Thus, microgravity induces bone deficits in rodents and primates likely through the suppression of bone formation.

scholarly journals Biaxial Normal Strength Behavior in the Axial-Transverse Plane for Human Trabecular Bone—Effects of Bone Volume Fraction, Microarchitecture, and Anisotropy

2013 ◽  
Vol 135 (12) ◽  
Author(s):  
Arnav Sanyal ◽  
Tony M. Keaveny
Keyword(s):  
Trabecular Bone ◽  
Volume Fraction ◽  
Elastic Anisotropy ◽  
Bone Volume ◽  
Transverse Plane ◽  
Mechanical Anisotropy ◽  
Bone Volume Fraction ◽  
Human Trabecular Bone ◽  
Strength Behavior ◽  
Normal Strength

The biaxial failure behavior of the human trabecular bone, which has potential relevance both for fall and gait loading conditions, is not well understood, particularly for low-density bone, which can display considerable mechanical anisotropy. Addressing this issue, we investigated the biaxial normal strength behavior and the underlying failure mechanisms for human trabecular bone displaying a wide range of bone volume fraction (0.06–0.34) and elastic anisotropy. Micro-computed tomography (CT)-based nonlinear finite element analysis was used to simulate biaxial failure in 15 specimens (5 mm cubes), spanning the complete biaxial normal stress failure space in the axial-transverse plane. The specimens, treated as approximately transversely isotropic, were loaded in the principal material orientation. We found that the biaxial stress yield surface was well characterized by the superposition of two ellipses—one each for yield failure in the longitudinal and transverse loading directions—and the size, shape, and orientation of which depended on bone volume fraction and elastic anisotropy. However, when normalized by the uniaxial tensile and compressive strengths in the longitudinal and transverse directions, all of which depended on bone volume fraction, microarchitecture, and mechanical anisotropy, the resulting normalized biaxial strength behavior was well described by a single pair of (longitudinal and transverse) ellipses, with little interspecimen variation. Taken together, these results indicate that the role of bone volume fraction, microarchitecture, and mechanical anisotropy is mostly accounted for in determining the uniaxial strength behavior and the effect of these parameters on the axial-transverse biaxial normal strength behavior per se is minor.

Architectural changes of trabecular bone caused by the remodeling process

2005 ◽  
Vol 874 ◽  
Author(s):  
Richard Weinkamer ◽  
Markus A. Hartmann ◽  
Yves Brechet ◽  
Peter Fratzl
Keyword(s):  
Trabecular Bone ◽  
Feedback Loop ◽  
Mechanical Response ◽  
Volume Fraction ◽  
Bone Volume ◽  
Bone Architecture ◽  
Mechanical Problem ◽  
Bone Volume Fraction ◽  
Obvious Effect ◽  
Trabecular Bone Architecture

AbstractUsing a stochastic lattice model we have studied the architectural changes of trabecular bone occurring while the structure is remodeled. Our model considers the mechanical feedback loop, which control the remodeling process. A fast algorithm was employed to solve approximately the mechanical problem. A general feature of the model is that a networklike structure emerges, which further coarsens while the bone volume fraction remains unchanged. Decreasing the mechanical response of the system by either lowering the external load or the internal mechano-sensitivity leads not only to a reduction of the bone volume fraction, but results in topological changes of the trabecular bone architecture, where the loss of horizontal trabeculae is the most obvious effect.

scholarly journals The plate-to-rod transition in trabecular bone loss is elusive

2021 ◽  
Vol 8 (6) ◽  
pp. 201401
Author(s):  
A. A. Felder ◽  
S. Monzem ◽  
R. De Souza ◽  
B. Javaheri ◽  
D. Mills ◽  
...  
Keyword(s):  
Bone Loss ◽  
Trabecular Bone ◽  
Volume Fraction ◽  
Bone Volume ◽  
Continuous Measure ◽  
Bone Volume Fraction ◽  
Trabecular Bone Loss ◽  
Mouse Tibia ◽  
Disease Stages ◽  
The Relationship

Changes in trabecular micro-architecture are key to our understanding of osteoporosis. Previous work focusing on structure model index (SMI) measurements have concluded that disease progression entails a shift from plates to rods in trabecular bone, but SMI is heavily biased by bone volume fraction. As an alternative to SMI, we proposed the ellipsoid factor (EF) as a continuous measure of local trabecular shape between plate-like and rod-like extremes. We investigated the relationship between EF distributions, SMI and bone volume fraction of the trabecular geometry in a murine model of disuse osteoporosis as well as from human vertebrae of differing bone volume fraction. We observed a moderate shift in EF median (at later disease stages in mouse tibia) and EF mode (in the vertebral samples with low bone volume fraction) towards a more rod-like geometry, but not in EF maximum and minimum. These results support the notion that the plate to rod transition does not coincide with the onset of bone loss and is considerably more moderate, when it does occur, than SMI suggests. A variety of local shapes not straightforward to categorize as rod or plate exist in all our trabecular bone samples.

scholarly journals Retaining Residual Ovarian Tissue following Ovarian Failure Has Limited Influence on Bone Loss in Aged Mice

2010 ◽  
Vol 2010 ◽  
pp. 1-6
Author(s):  
Zelieann R. Craig ◽  
Samuel L. Marion ◽  
Janet L. Funk ◽  
Mary L. Bouxsein ◽  
Patricia B. Hoyer
Keyword(s):  
Bone Loss ◽  
Volume Fraction ◽  
Ovarian Tissue ◽  
Ovarian Failure ◽  
Bone Volume ◽  
Bone Volume Fraction ◽  
Trabecular Thickness ◽  
Ct Analysis ◽  
Time Point ◽  
Young Mice

Previous work showed that retaining residual ovarian tissue protects young mice from accelerated bone loss following ovarian failure. The present study was designed to determine whether this protection is also present in aged animals. Aged (9–12 months) C57BL/6Hsd female mice were divided into: CON (vehicle), VCD (160 mg/kg; 15d), or OVX (ovariectomized). Lumbar BMD was monitored by DXA andμCT used to assess vertebral microarchitecture. BMD was not different between VCD and CON at any time point but was lower (P<.05) than baseline, starting 1 month after ovarian failure in VCD and OVX mice. FollowingμCT analysis there were no differences between CON and VCD, but OVX mice had lower bone volume fraction, trabecular thickness, and a trend for decreased connectivity density. These findings provide evidence that retention of residual ovarian tissue may protect aged follicle-depleted mice from accelerated bone loss to a lesser extent than that observed in young mice.

Whole human vertebral body BMD and bone volume fraction examined by DXA and micro-CT

Bone ◽  
2009 ◽  
Vol 44 ◽  
pp. S375
Author(s):  
E. Perilli⁎ ◽  
A.M. Briggs ◽  
J.D. Wark ◽  
S. Kantor ◽  
I.H. Parkinson ◽  
...  
Keyword(s):  
Vertebral Body ◽  
Volume Fraction ◽  
Bone Volume ◽  
Micro Ct ◽  
Bone Volume Fraction

Influence of bone volume fraction and architecture on computed large-deformation failure mechanisms in human trabecular bone

Bone ◽  
2006 ◽  
Vol 39 (6) ◽  
pp. 1218-1225 ◽  
Author(s):  
Grant Bevill ◽  
Senthil K. Eswaran ◽  
Atul Gupta ◽  
Panayiotis Papadopoulos ◽  
Tony M. Keaveny
Keyword(s):  
Trabecular Bone ◽  
Large Deformation ◽  
Volume Fraction ◽  
Failure Mechanisms ◽  
Bone Volume ◽  
Bone Volume Fraction ◽  
Human Trabecular Bone

Misalignment Error in Cancellous Bone Apparent Elastic Modulus Depends on Bone Volume Fraction and Degree of Anisotropy

2020 ◽  
Vol 143 (2) ◽  
Author(s):  
Matthew B. L. Bennison ◽  
A. Keith Pilkey ◽  
W. Brent Lievers
Keyword(s):  
Mechanical Properties ◽  
Elastic Modulus ◽  
Cancellous Bone ◽  
Volume Fraction ◽  
Experimental Studies ◽  
Bone Volume ◽  
Bone Volume Fraction ◽  
Skeletal Site ◽  
Degree Of Anisotropy ◽  
Misalignment Error

Abstract Cancellous bone is an anisotropic structure with architectural and mechanical properties that vary due to both skeletal site and disease state. This anisotropy means that, in order to accurately and consistently measure the mechanical properties of cancellous bone, experiments should be performed along the primary mechanical axis (PMA), that is, the orientation in which the mechanical properties are at their maximum value. Unfortunately, some degree of misalignment will always be present, and the magnitude of the resulting error is expected to be architecture dependent. The goal of this work is to quantify the dependence of the misalignment error, expressed in terms of change in apparent elastic modulus (ΔE), on both the bone volume fraction (BV/TV) and the degree of anisotropy (DA). Finite element method (FEM) models of bovine cancellous bone from five different skeletal sites were created at 5 deg and 20 deg from the PMA determined for each region. An additional set of models was created using image dilation/erosion steps in order to control for BV/TV and better isolate the effect of DA. Misalignment error was found to increase with increasing DA and decreasing BV/TV. At 5 deg misaligned from the PMA, error is relatively low (&lt;5%) in all cases but increases to 8–24% error at 20 deg. These results suggest that great care is needed to avoid introducing misalignment error into experimental studies, particularly when studying regions with high anisotropy and/or low bone volume fraction, such as vertebral or osteoporotic bone.

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