Pressure gradients and transport in the murine femur upon hindlimb suspension

Stevens, Hazel Y.; Meays, Diana; Frangos, John A.

doi:10.1016/j.bone.2006.03.007

Cited by 55 publications

(62 citation statements)

References 34 publications

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“…It is possible that the rapid change in intramedullary pressure creates swift alterations in a pressure gradient which in turn drive the interstitial flow in the lacunocanalicular network. Our measurement of the baseline intramedullary pressure of approximately 10 mmHg is in good agreement to the data published by Stevens et al [25]. Although the observed pressure alteration with knee loading is 0.2 ~ 10% of the baseline intramedullary pressure, it is a dynamic change rather than static.…”

Section: Discussionsupporting

confidence: 81%

Knee loading dynamically alters intramedullary pressure in mouse femora

Zhang

Liu

et al. 2007

Bone

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Dynamic mechanical loads have been known to stimulate bone formation. Many biophysical factors such as number of daily loading cycles, bone strain, strain-induced interstitial fluid flow, molecular transport, and modulation of intramedullary pressure have been considered as potential mediators in mechanotransduction of bone. Using a knee loading modality that enhances anabolic responses in mouse hindlimb, we addressed a question: Do oscillatory loads applied to the knee induce dynamic alteration of intramedullary pressure in the femoral medullary cavity? To answer this question, mechanical loads were applied to the knee with a custom-made piezoelectric loader and intramedullary pressure in the femoral medullary cavity was measured with a fiber optic pressure sensor. We observed that in response to sinusoidal forces of 0.5 Hz and 10 Hz, pressure amplitude increased up to 4-N loads and reached a plateau at 130 Pa. This amplitude significantly decreased with a loading frequency above 20 Hz. To confirm alteration of intramedullary pressure, real-time motion of microparticles in a glass tube inserted to the femoral medullary cavity ex vivo was visualized. Taken together, these data reveal that knee loading dynamically alters intramedullary pressure as a function of loading intensities and frequencies.

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Section: Discussionsupporting

confidence: 81%

Knee loading dynamically alters intramedullary pressure in mouse femora

Zhang

Liu

et al. 2007

Bone

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“…However, together with previous biomechanics studies using fluorescence recovery after photobleaching (FRAP) [21] and fiber optical pressure sensors [9,12,13] they allow us to consider a certain biophysical model. FRAP data are consistent with load-driven fluid flow, while pressure data support alterations of intramedullary pressure in response to mechanical loading.…”

Section: Discussionmentioning

confidence: 99%

“…In separate loading studies, augmentation of intramedullary pressure through an external pressure source has also been shown to increase bone formation using in vivo turkey ulnae [10,11]. Similarly, a pressure gradient, elevated by venous ligation, was shown to increase interstitial fluid flow and this flow-mediated bone adaptation was considered to be independent of mechanical strain [12][13][14]. Alteration of intramedullary pressure is therefore likely to be a potential mediator for knee loading-driven bone formation [8].…”

Section: Introductionmentioning

confidence: 99%

Effects of surgical holes in mouse tibiae on bone formation induced by knee loading

Zhang

Yokota

2007

Bone

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Loads applied directly to the knee (knee loading) have recently been demonstrated to induce anabolic responses in femoral and tibial cortical bone. In order to examine the potential role of intramedullary pressure in generating those knee loading responses, we investigated the effects of drilling surgical holes that penetrated into the tibial medullary cavity and thereby modulated pressure alteration. Thirty-nine C57/BL/6 female mice in total were used with and without surgical holes, and the surgical holes were monitored with micro CT and histology. The left knee was loaded for 3 days, and the contralateral limb was treated as a sham-loaded control. Mice were sacrificed for bone histomorphometry 2 weeks after the last loading. Although the surgical hole induced bone formation in both loaded and non-loaded tibiae, due to regional and systemic acceleratory phenomenon the anabolic effect of knee loading was substantially diminished. Without the holes, knee loading significantly elevated cross-sectional cortical area, cortical thickness, mineralizing surface, mineral apposition rate, and bone formation rate on the periosteal surface. For example, the rate of bone formation was elevated 2.1 fold (p < 0.001; middle diaphysis -50% site from the knee along the length of tibiae) and 2.7 fold (p < 0.01; distal diaphysis -75% site). With the surgical holes, however, knee loading did not provide significant enhancement either at the 50% or 75% site in any of the histomorphometric measurements (p > 0.05). The results support the idea that alteration of intramedullary pressure is necessary for knee loading to induce bone formation in the diaphysis.

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“…It has been suggested that the loss of bone observed during disuse is the result of osteocyte hypoxia, resulting from unloading that reduces the interstitial fluid flow and, consequentially, reduces oxygen transport (18,19). It is widely regarded that disruption of the lacuno-canalicular network, which is necessary for nutrient and gaseous exchange for osteocytes, results in localized hypoxia in bone (20,21).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia mediates osteocyte ORP150 expression and cell death in vitro

Montesi

Jähn

Bonewald

et al. 2016

Molecular Medicine Reports

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Abstract. Skeletal unloading leads to hypoxia in the bone microenvironment, resulting in imbalanced bone remodeling that favors bone resorption. Osteocytes, the mechanosensors of bone, have been demonstrated to orchestrate bone homeostasis. Hypoxic osteocytes either undergo apoptosis or actively stimulate osteoclasts to remove bone matrix during hypoxia. Oxygen-regulated protein 150 (ORP150) is an endoplasmic reticulum-associated chaperone that has been observed to serve an important role in the cellular adaptation to hypoxia and in preventing cellular apoptosis in various tissue types. The current study hypotheses that expression of ORP150 would be increased in osteocytes under hypoxic conditions (1% O 2 ). The MLO-Y4 osteocyte cell line was cultured under normoxic or hypoxic conditions for up to 72 h. It was demonstrated that 1% O 2 significantly induced hypoxia after 16 h and up to 72 h, significantly reduced cell number at 8 and 48 h, induced cell death at 8, 24 and 48 h and induced apoptosis at 16, 24 and 48 h. Significant differences in ORP150 mRNA were observed at 72 h, however no differences were observed in the protein expression levels. The relative increase in ORP150 mRNA observed in hypoxia, compared with normoxia, may support its cytoprotective role in oxygen-deprived conditions.

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Pressure gradients and transport in the murine femur upon hindlimb suspension

Cited by 55 publications

References 34 publications

Knee loading dynamically alters intramedullary pressure in mouse femora

Knee loading dynamically alters intramedullary pressure in mouse femora

Effects of surgical holes in mouse tibiae on bone formation induced by knee loading

Hypoxia mediates osteocyte ORP150 expression and cell death in vitro

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