Effects of Rehydration State on the Flexural Properties of Whole Mouse Long Bones

Broz, Jerry J.; Simske, Steven J.; Greenberg, Alan R.; Luttges, Marvin W.

doi:10.1115/1.2895510

Cited by 67 publications

(47 citation statements)

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“…Testing was performed using an Instron Dynamite 8841 servo-hydraulic materials testing device equipped with a 1 kN load cell, with control and data collection using Bluehill software version 1.8 (Instron, Norwood, MA). Prior to testing, each femur was harvested and cleaned of soft-tissue and soaked in PBS for 3 hours to ensure hydration (Broz et al, 1993). The anterior surface of each femur was placed on the two support beams, which were separated by an 8-mm span.…”

Section: Mechanical Testingmentioning

confidence: 99%

Axin2 controls bone remodeling through the β-catenin–BMP signaling pathway in adult mice

Yan

Tang

Chen

et al. 2009

Journal of Cell Science

111

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To investigate the role of Wnt–β-catenin signaling in bone remodeling, we analyzed the bone phenotype of female Axin2-lacZ knockout (KO) mice. We found that trabecular bone mass was significantly increased in 6- and 12-month-old Axin2 KO mice and that bone formation rates were also significantly increased in 6-month-old Axin2 KO mice compared with wild-type (WT) littermates. In vitro studies were performed using bone marrow stromal (BMS) cells isolated from 6-month-old WT and Axin2 KO mice. Osteoblast proliferation and differentiation were significantly increased and osteoclast formation was significantly reduced in Axin2 KO mice. Nuclear β-catenin protein levels were significantly increased in BMS cells derived from Axin2 KO mice. In vitro deletion of the β-catenin gene under Axin2 KO background significantly reversed the increased alkaline phosphatase activity and the expression of osteoblast marker genes observed in Axin2 KO BMS cells. We also found that mRNA expression of Bmp2 and Bmp4 and phosphorylated Smad1/5 protein levels were significantly increased in BMS cells derived from Axin2 KO mice. The chemical compound BIO, an inhibitor of glycogen synthase kinase 3β, was utilized for in vitro signaling studies in which upregulated Bmp2 and Bmp4 expression was measured in primary calvarial osteoblasts. Primary calvarial osteoblasts were isolated from Bmp2fx/fx;Bmp4fx/fx mice and infected with adenovirus-expressing Cre recombinase. BIO induced Osx, Col1, Alp and Oc mRNA expression in WT cells and these effects were significantly inhibited in Bmp2/4-deleted osteoblasts, suggesting that BIO-induced Osx and marker gene expression were Bmp2/4-dependent. We further demonstrated that BIO-induced osteoblast marker gene expression was significantly inhibited by Osx siRNA. Taken together, our findings demonstrate that Axin2 is a key negative regulator in bone remodeling in adult mice and regulates osteoblast differentiation through the β-catenin–BMP2/4–Osx signaling pathway in osteoblasts.

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Section: Mechanical Testingmentioning

confidence: 99%

Axin2 controls bone remodeling through the β-catenin–BMP signaling pathway in adult mice

Yan

Tang

Chen

et al. 2009

Journal of Cell Science

111

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“…Analysis of the photographs was used to calculate bone formation rate (BFR) for both the periosteal (Ps.BFR) and endocortical (Ec.BFR) surfaces (26). Bone formation rate was calculated as the product of mineralized surface (MS) and mineral apposition rate (MAR).…”

Section: Quantitative Histomorphometrymentioning

confidence: 99%

Long-Term Dose Response of Trabecular Bone in Mice to Proton Radiation

et al. 2008

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Astronauts on exploratory missions will experience a complex environment, including microgravity and radiation. While the deleterious effects of unloading on bone are well established, fewer studies have focused on the effects of radiation. We previously demonstrated that 2 Gy of ionizing radiation has deleterious effects on trabecular bone in mice 4 months after exposure. The present study investigated the skeletal response after total doses of proton radiation that astronauts may be exposed to during a solar particle event. We exposed mice to 0.5, 1 or 2 Gy of whole-body proton radiation and killed them humanely 117 days later. Tibiae and femora were analyzed using microcomputed tomography, mechanical testing, mineral composition and quantitative histomorphometry. Relative to control mice, mice exposed to 2 Gy had significant differences in trabecular bone volume fraction (−20%), trabecular separation (+11%), and trabecular volumetric bone mineral density (−19%). Exposure to 1 Gy radiation induced a nonsignificant trend in trabecular bone volume fraction (−13%), while exposure to 0.5 Gy resulted in no differences. No response was detected in cortical bone. Further analysis of the 1-Gy mice using synchrotron microCT revealed a significantly lower trabecular bone volume fraction (−13%) than in control mice. Trabecular bone loss 4 months after exposure to 1 Gy highlights the importance of further examination of how space radiation affects bone.

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“…For biomechanical testing of the femora, bones were rehydrated in PBS for 90 min before evaluation to simulate in vivo properties (7). Three-point bending tests were performed using an Instron 5582 (BlueHill 2 software, Instron, Norwood, MA).…”

Section: Biomechanical Testingmentioning

confidence: 99%

Development of a low-dose anti-resorptive drug regimen reveals synergistic suppression of bone formation when coupled with disuse

Lloyd¹,

Travis²,

Lu³

et al. 2008

Journal of Applied Physiology

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Lloyd SAJ, Travis ND, Lu T, Bateman TA. Development of a low-dose anti-resorptive drug regimen reveals synergistic suppression of bone formation when coupled with disuse. J Appl Physiol 104: 729-738, 2008. First published January 3, 2007 doi:10.1152/japplphysiol.00632.2007.-Safe and effective countermeasures to spaceflight-induced osteoporosis are required to mitigate the potential for mission-critical fractures and ensure long-term bone health in astronauts. Two anti-resorptive drugs, the bisphosphonate zoledronic acid (ZOL) and the anti-receptor activator of NF-B ligand protein osteoprotegerin (OPG), were investigated to find the minimum, comparable doses that yield a maximal increase in bone quality, while minimizing deleterious effects on turnover and mineralization. Through a series of five trials in normally loaded female mice (n ϭ 56/trial), analysis of trabecular volume fraction and connectivity using microcomputed tomography, along with biomechanical testing, quantitative histomorphometry, and compositional analysis, was used to select 45 g/kg ZOL and 500 g/kg OPG as doses that satisfy these criteria. These doses were then examined for their ability to mitigate bone loss following short-term unloading through hindlimb suspension (HLS). Seventy-two mice were prophylactically administered ZOL, OPG, or PBS and assigned to loaded control or 2-wk HLS groups (n ϭ 12 for each of 6 groups). Both anti-resorptives were able to preserve trabecular microarchitecture and femoral elastic and maximum force in HLS mice (ϩ30 -40% ZOL/OPG vs. PBS). In HLS mice, anti-resorptive dosing reduced resorption perimeter at the femoral endocortical surface by 30% vs. PBS. In loaded control mice, anti-resorptives produced no change in bone formation rate; however, reductions in bone formation rate brought about by HLS were exacerbated by anti-resorptive treatment, suggesting synergistic inhibition of osteoblasts during disuse. Refined anti-resorptive dosing will tend to target countermeasures to the period of disuse, resulting in faster recovery and less adverse effects for astronauts. spaceflight; osteoprotegerin; zoledronic acid; osteoporosis; bone loss; microcomputed tomography THE "VISION FOR SPACE exploration" has directed the National Aeronautics and Space Administration (NASA) toward human exploration of the Moon and Mars within the next 30 years (22). In addition to the many engineering challenges associated with such an undertaking, there are important biomedical issues that result from extended exposure to the space environment, including muscle atrophy (35), altered immune function (39), and metabolic disruptions (24). The risk of bone loss is also a major obstacle for the future of long-duration spaceflight (34,36).In microgravity, skeletal unloading causes increased bone resorption, which leads to long-term demineralization of loadbearing bones (34). Astronauts experience an average net loss of ϳ230 mg calcium/day (33). Bone loss at a rate of 0.5-2.0%/mo in load-bearing bones creates a risk of fractures during the mi...

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Effects of Rehydration State on the Flexural Properties of Whole Mouse Long Bones

Cited by 67 publications

References 0 publications

Axin2 controls bone remodeling through the β-catenin–BMP signaling pathway in adult mice

Axin2 controls bone remodeling through the β-catenin–BMP signaling pathway in adult mice

Long-Term Dose Response of Trabecular Bone in Mice to Proton Radiation

Development of a low-dose anti-resorptive drug regimen reveals synergistic suppression of bone formation when coupled with disuse

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