Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: A new model to study cortical and cancellous compartments in a single loaded element

Souza, Roberto Lopes de; Matsuura, Maiko; Eckstein, F.; Rawlinson, Simon C.F.; Lanyon, Lance E.; Pitsillides, Andrew A.

doi:10.1016/j.bone.2005.07.022

Cited by 348 publications

(489 citation statements)

References 47 publications

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“…Mechanical Loading of the Mouse Tibia in Vivo-The right tibia of 32 female C57BL/6 mice (15 weeks old) and 24 female ER␣ Ϫ/Ϫ mice were subjected to single period of dynamic axial load using a hydraulic actuator under feedback control (38) (Dartec HC10, Zwick/Roell UK). The load was applied with a sine waveform, at a frequency of 2 Hz for 30 s (60 cycles).…”

Section: Methodsmentioning

confidence: 99%

Wnt/β-Catenin Signaling Is a Component of Osteoblastic Bone Cell Early Responses to Load-bearing and Requires Estrogen Receptor α

Armstrong¹,

Muzylak

Sunters

et al. 2007

Journal of Biological Chemistry

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259

226

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The Wnt/␤-catenin pathway has been implicated in bone cell response to their mechanical environment. This response is the origin of the mechanism by which bone cells adjust bone architecture to maintain bone strength. Osteoporosis is the most widespread failure of this mechanism. The degree of osteoporotic bone loss in men and women is related to bio-available estrogen. Here we report that in osteoblastic ROS 17/2.8 cells and primary osteoblast cultures, a single short period of dynamic mechanical strain, as well as the glycogen synthase kinase-3␤ (GSK-3␤) inhibitor LiCl, increased nuclear accumulation of activated ␤-catenin and stimulated TCF/LEF reporter activity. This effect was blocked by the estrogen receptor (ER) modulators ICI 182,780 and tamoxifen and was absent in primary osteoblast cultures from mice lacking ER␣. Microarray expression data for 25,000 genes from total RNA extracted from tibiae of wild-type mice within 24 h of being loaded in vivo showed differential gene regulation between loaded and contralateral non-loaded bones of 10 genes established to be involved in the Wnt pathway. Only 2 genes were involved in loaded tibiae from mice lacking ER␣ (ER␣ ؊/؊ ). Together these data suggest that Wnt/␤-catenin signaling contributes to bone cell early responses to mechanical strain and that its effectiveness requires ER␣. Reduced effectiveness of bone cell responses to bone loading, associated with estrogen-related decline in ER␣, may contribute to the failure to maintain structurally appropriate bone mass in osteoporosis in both men and women.

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Section: Methodsmentioning

confidence: 99%

Wnt/β-Catenin Signaling Is a Component of Osteoblastic Bone Cell Early Responses to Load-bearing and Requires Estrogen Receptor α

Armstrong¹,

Muzylak

Sunters

et al. 2007

Journal of Biological Chemistry

Self Cite

259

226

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show abstract

“…Protocols using external compressive loading of the rat or mouse ulna have explored the roles of strain magnitude [106][107], strain rate [108], and loading bout frequency and duration [109]. In general, bone formation exhibits a positive dose-response relationship with peak strain magnitude [106][107][110][111]. However, peak strains need only approximate the high end of physiological values (rather than be excessive) to trigger bone formation [106][107].…”

Section: Bone Response To Trainingmentioning

confidence: 99%

Muscle and bone plasticity after spinal cord injury: Review of adaptations to disuse and to electrical muscle stimulation

Dudley-Javoroski

Shields

2008

JRRD

164

141

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Abstract-The paralyzed musculoskeletal system retains a remarkable degree of plasticity after spinal cord injury (SCI). In response to reduced activity, muscle atrophies and shifts toward a fast-fatigable phenotype arising from numerous changes in histochemistry and metabolic enzymes. The loss of routine gravitational and muscular loads removes a critical stimulus for maintenance of bone mineral density (BMD), precipitating neurogenic osteoporosis in paralyzed limbs. The primary adaptations of bone to reduced use are demineralization of epiphyses and thinning of the diaphyseal cortical wall. Electrical stimulation of paralyzed muscle markedly reduces deleterious post-SCI adaptations. Recent studies demonstrate that physiological levels of electrically induced muscular loading hold promise for preventing post-SCI BMD decline. Rehabilitation specialists will be challenged to develop strategies to prevent or reverse musculoskeletal deterioration in anticipation of a future cure for SCI. Quantifying the precise dose of stress needed to efficiently induce a therapeutic effect on bone will be paramount to the advancement of rehabilitation strategies.

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“…This makes HF mechanical loading a powerful non-pharmacological intervention not only for the treatment or prevention of osteoporosis but also for fracture healing and beyond [1,19,20]. Numerous in vivo systems employing HF loading have been successfully used, such as whole body vibration (WBV) devices [16][17][18] and individual limb compressive loading setups [21,22]. WBV experiments have evidenced the advantageous effects of HF loading on bone [16][17][18] and on titanium implant osseointegration [23].…”

Section: Introductionmentioning

confidence: 99%

High-frequency loading positively impacts titanium implant osseointegration in impaired bone

et al. 2014

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Summary High-frequency loading via whole body vibration promotes bone formation and increases bone strength. Whether this translates to positive titanium implant osseointegration in osteoporotic bone was explored in this animal study. An anabolic effect of not only bisphosphonate treatment but also high-frequency loading on implant osseointegration in osteoporotic bone was observed. Introduction The present study investigated the impact of high-frequency (HF) loading, applied via whole body vibration (WBV), on titanium implant osseointegration in healthy versus ovariectomyinduced compromised versus pharmacologically treated compromised bone. Methods A custom-made Ti implant was inserted into the metaphyseal tibia of 59 rats and left to heal for either 4 or 14 days. Rats were divided into six groups according to their hormonal and mechanical status. WBV, consisting of 10 consecutive frequency steps at an acceleration of 0.3g, was applied daily for either 4 or 14 days. Tissue samples were processed for quantitative histology at the tibial cortical and medullar level. Data were analyzed by three-way ANOVA and by post hoc pairwise comparisons. Results The bone healing response at the interface and surrounding titanium implants was negatively influenced by osteoporotic bone conditions, mainly at the trabecular bone level. Furthermore, the administration of bisphosphonates for preventing the ovariectomy-induced impaired periimplant response was successful. Finally, the effect of HF WBV loading on the peri-implant bone healing was dependent on the bone condition and was anabolic solely in untreated osteoporotic trabecular bone when applied for an extended period of time. ConclusionsThe bone healing response to implant installation is compromised in osteoporotic bone conditions, in particular at the trabecular bone compartment. Meanwhile, not only pharmacological treatment but also mechanical loading via HF WBV can exert a positive effect on implant osseointegration in this specific bone micro-environment. The peri-implant cortical bone, however, seems to be less sensitive to HF WBV loading influences.

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Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: A new model to study cortical and cancellous compartments in a single loaded element

Cited by 348 publications

References 47 publications

Wnt/β-Catenin Signaling Is a Component of Osteoblastic Bone Cell Early Responses to Load-bearing and Requires Estrogen Receptor α

Wnt/β-Catenin Signaling Is a Component of Osteoblastic Bone Cell Early Responses to Load-bearing and Requires Estrogen Receptor α

Muscle and bone plasticity after spinal cord injury: Review of adaptations to disuse and to electrical muscle stimulation

High-frequency loading positively impacts titanium implant osseointegration in impaired bone

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