Induced Intramedullary Pressure by Dynamic Hydraulic Stimulation and Its Potential in Attenuation of Bone Loss

2011 ◽  
Author(s):  
M. Hu ◽  
J. Cheng ◽  
S. Ferreri ◽  
F. Serra-Hsu ◽  
W. Lin ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Bone Loss ◽  
Bone Adaptation ◽  
Dependent Manner ◽  
Hydraulic Stimulation ◽  
Flow Coupling ◽  
Bone Fluid Flow ◽  
Intramedullary Pressure ◽  
New Treatments

Bone loss is a critical health problem of astronauts in long-term space missions. A growing number of evidence has pointed out bone fluid flow as a critical regulator in mechanotransductive signaling and bone adaptation. Intramedullary pressure (ImP) is a key mediator for bone fluid flow initiation and it influences the osteogenic signals within the skeleton. The potential ImP-induced bone fluid flow then triggers bone adaptation [1]. Previous in vivo study has demonstrated that ImP induced by oscillatory electrical stimulations can effectively mitigate disuse osteopenia in a frequency-dependent manner in a disuse rat model [2, 3]. In order to develop the translational potentials of ImP, a non-invasive intervention with direct fluid flow coupling is necessary to develop new treatments for microgravity-induced osteopenia/osteoporosis.

Local and Distant Intramedullary Pressure and Bone Strain by Dynamic Hydraulic Stimulation

2011 ◽  
Author(s):  
Y. X. Qin ◽  
M. Hu ◽  
F. Serra-Hsu ◽  
J. Cheng ◽  
S. Ferreri ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Bone Adaptation ◽  
External Loading ◽  
Bone Strain ◽  
Dependent Manner ◽  
Frequency Dependent ◽  
Hydraulic Stimulation ◽  
Bone Fluid Flow ◽  
Intramedullary Pressure ◽  
Osteogenic Response

Osteoporosis gives rise to fragile bones that have higher fracture risks due to diminished bone mass and altered bone microarchitecture [1]. Mechanical loading mediated bone adaptation has demonstrated promising potentials as a non-pharmacological alteration for both osteogenic response and attenuation of osteopenia [2]. Intramedullary pressure (ImP) has been proposed as a key factor for fluid flow initiation and mechanotransductive signal inductions in bone. It is also suggested that integration of strain signals over time allows low-level mechanical strain in the skeleton to trigger osteogenic activities. The potential bone fluid flow induced by strain and ImP mediates adaptive responses in the skeleton [3]. Previous in vivo studies using oscillatory electrical stimulations showed that dynamic muscle contractions can generate ImP and bone strain to mitigate disuse osteopenia in a frequency-dependent manner. To apply ImP alteration as a means for bone fluid flow regulation, it may be necessary to develop a new method that could couple external loading with internal bone fluid flow. In order to further study the direct effect of ImP on bone adaptation, it was hypothesized that external dynamic hydraulic stimulation (DHS) can generate ImP with minimal strain in a frequency-dependent manner. The aim of this study was to evaluate the immediate effects on local and distant ImP and bone strain induced by a novel, non-invasive dynamic external pressure stimulus in response to a range of loading frequencies.

In Vivo Mesenchymal Stem Cell Proliferation in Response to Dynamic Fluid Flow Stimulation

2012 ◽  
Author(s):  
M. Hu ◽  
R. Yeh ◽  
M. Lien ◽  
Y. X. Qin
Keyword(s):  
Fluid Flow ◽  
Bone Tissue ◽  
Bone Adaptation ◽  
Hindlimb Suspension ◽  
Osteoporotic Bone ◽  
Hydraulic Stimulation ◽  
Structural Deterioration ◽  
Bone Fluid Flow ◽  
Cord Injury

Osteoporosis is a debilitating disease characterized as decreased bone mass and structural deterioration of bone tissue. Osteoporotic bone tissue turns itself into altered structure, which leads to weaker bones that are more susceptible for fractures. While often happening in elderly, long-term bed-rest patients, e.g. spinal cord injury, and astronauts who participate in long-duration spaceflights, osteoporosis has been considered as a major public health thread and causes great medical cost impacts to the society. Mechanobiology and novel stimulation on regulating bone health have long been recognized. Loading induced bone fluid flow, as a critical mechanotransductive promoter, has been demonstrated to regulate cellular signaling, osteogenesis, and bone adaptation [4]. As one of the factors that mediate bone fluid flow, intromedullary pressure (ImP) creates a pressure gradient that further influence the magnitude of mechanotransductory signals [5]. As for a potential translational development of ImP, our group has recently introduced a novel, non-invasive dynamic hydraulic stimulation (DHS) on bone structural enhancement. Its promising effects on inhibition of disuse bone loss has been shown with 2 Hz loading through a 4-week hindlimb suspension rat study followed by microCT analysis. At the cellular level, mesenchymal stem cells (MSCs) are defined by their self-renewal ability and that to potentially differentiate into the cells that form tissues such as bone [1]. To further elucidate the cellular effects of DHS and its potential mechanism on bone quality enhancement, the objective of this study was to measure MSC quantification in response to the in vivo mechanical signals driven by DHS.

Inhibition of Bone Loss and Muscle Atrophy by Dynamic Muscle Contractions With Rest Periods in a Functional Disuse Mouse Model

2008 ◽  
Author(s):  
Adiba Ali ◽  
Yi-Xian Qin
Keyword(s):  
Bone Loss ◽  
Mouse Model ◽  
Muscle Atrophy ◽  
High Frequency ◽  
Synergistic Effects ◽  
Bone Adaptation ◽  
Muscle Contractions ◽  
Rest Periods ◽  
Bone Fluid Flow ◽  
Intramedullary Pressure

Osteoporosis, induced by aging and long-term disuse, often occurs together with muscle loss. Musculoskeletal disuse causes severe physiologic changes and it has been proposed the synergistic effects of muscle function and bone adaptation. Bone fluid flow has been shown to be induced during mechanical loading, and is proposed to be a critical mediator of bone adaptation. The skeletal muscle may serve as a muscle pump that may mediate bone mechanotransduction via modulation of intramedullary pressure. Thus, muscular stimulation is proposed to be used to simultaneously treat both muscle and bone loss, but the optimal parameters required for such treatment is unclear. Studies have separately investigated the optimal signal parameters for bone or muscle. Insertion of recovery periods during high frequency stimulations have shown potential to reduce muscle atrophy by minimizing fatigue and mimicking physiologic contractions, and demonstrated enhancement of bone remodeling. Our preliminary research has indicated that dynamic muscle contractions within an optimal frequency range can significantly recover disuse induced bone loss. However, the optimal rest periods required to prevent muscle fatigue during stimulations are not clear. The overall objective of this study was to evaluate optimized dynamic muscle stimulations at relatively high frequency, e.g., 20 Hz, and to test the role of varying the rest duration on muscle mass and bone morphology in a functional hind limb disuse mouse model.

The Effects of Loading Rate and Duration on Mitigation of Osteopenia by Dynamic Muscle Stimulation

2009 ◽  
Author(s):  
Yi-Xian Qin ◽  
Hoyan Lam ◽  
Murtaza Malbari
Keyword(s):  
Bone Loss ◽  
Muscle Atrophy ◽  
High Frequency ◽  
Synergistic Effects ◽  
Bone Adaptation ◽  
Muscle Adaptation ◽  
Skeletal Health ◽  
Skeletal Tissue ◽  
Bone Fluid Flow ◽  
Intramedullary Pressure

Musculoskeletal adaptations to aging and disuse environment have significant physiological effects on skeletal health, i.e., osteopenia and bone loss. Osteoporosis often occurs together with muscle loss. Such musculoskeletal complications cause severe physiologic changes and have been proposed the synergistic effects of muscle function and bone adaptation. The role of mechanobiology in the skeletal tissue may be closely related to load-induced transductive signals, e.g., bone fluid flow, which is proposed to be a critical mediator of bone and muscle adaptation. The skeletal muscle may serve as a muscle pump that may mediate bone mechanotransduction via modulation of intramedullary pressure. Muscular stimulation (MS) is proposed to be used to simultaneously treat both muscle and bone loss. Indeed, our recent data have demonstrated that high frequency, short duration stimulation can inhibit bone loss and muscle atrophy. Although 10 min dynamic loading can effectively attenuate bone loss, it cannot totally recover disuse osteopenia. The optimal parameters required for such treatment are unclear. Studies have separately investigated the optimal signal parameters for bone or muscle. Insertion of recovery periods during high frequency stimulations to extend the loading cycles have shown potential to reduce muscle atrophy by minimizing fatigue and mimicking physiologic contractions, and demonstrated enhancement of bone remodeling. The overall hypothesis for this study is that dynamic MS can enhance anabolic activity in bone, and inhibit bone loss in a functional disuse condition. Combined high frequency and sufficient loading cycle may be able to completely mitigate bone loss induced by disuse osteopenia.

scholarly journals Mechanotransduction in Musculoskeletal Tissue Regeneration: Effects of Fluid Flow, Loading, and Cellular-Molecular Pathways

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Yi-Xian Qin ◽  
Minyi Hu
Keyword(s):  
Fluid Flow ◽  
Bone Loss ◽  
Mechanical Loading ◽  
Tissue Regeneration ◽  
Underlying Mechanism ◽  
Bone Adaptation ◽  
Bone Tissue Regeneration ◽  
Molecular Pathways ◽  
Musculoskeletal Tissue ◽  
Mechanical Signals

While mechanotransductive signal is proven essential for tissue regeneration, it is critical to determine specific cellular responses to such mechanical signals and the underlying mechanism. Dynamic fluid flow induced by mechanical loading has been shown to have the potential to regulate bone adaptation and mitigate bone loss. Mechanotransduction pathways are of great interests in elucidating how mechanical signals produce such observed effects, including reduced bone loss, increased bone formation, and osteogenic cell differentiation. The objective of this review is to develop a molecular understanding of the mechanotransduction processes in tissue regeneration, which may provide new insights into bone physiology. We discussed the potential for mechanical loading to induce dynamic bone fluid flow, regulation of bone adaptation, and optimization of stimulation parameters in various loading regimens. The potential for mechanical loading to regulate microcirculation is also discussed. Particularly, attention is allotted to the potential cellular and molecular pathways in response to loading, including osteocytes associated with Wnt signaling, elevation of marrow stem cells, and suppression of adipotic cells, as well as the roles of LRP5 and microRNA. These data and discussions highlight the complex yet highly coordinated process of mechanotransduction in bone tissue regeneration.

scholarly journals Interrelation between external oscillatory muscle coupling amplitude and in vivo intramedullary pressure related bone adaptation

Bone ◽  
2014 ◽  
Vol 66 ◽  
pp. 178-181 ◽  
Author(s):  
Minyi Hu ◽  
Jiqi Cheng ◽  
Neville Bethel ◽  
Frederick Serra-Hsu ◽  
Suzanne Ferreri ◽  
...  
Keyword(s):  
Bone Adaptation ◽  
Intramedullary Pressure

scholarly journals Mitochondrial Phosphoenolpyruvate Carboxykinase (PCK2) Maintains the Function of Bone Marrow Mesenchymal Stromal/stem Cells to Rescue Osteoporotic Phenotype Partly Through Autophagy Dependent Manner

2020 ◽  
Author(s):  
Zheng Li ◽  
Xuenan Liu ◽  
Xuejiao Liu ◽  
Yangge Du ◽  
Yuan Zhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Loss ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Adipogenic Differentiation ◽  
Osteoporosis Treatment ◽  
Dependent Manner ◽  
Aged Mice ◽  
Stromal Stem Cells

Abstract BackgroundMitochondrial phosphoenolpyruvate carboxykinase (PCK2) is a rate-limiting enzyme that plays critical roles in multiple physiological processes. We unveiled the important role of PCK2 on the regulation of osteogenesis by mesenchymal stromal/stem cells (MSCs) in our previous work. Here we further investigated the roles of PCK2 on regulating adipogenesis of MSCs and its therapeutic effect on osteoporosis. MethodsWe investigated PCK2 function in adipogenic differentiation of MSCs in vitro through loss-and-gain-of-function experiments. This was followed by heterotopic adipose formation assay in nude mice. In addition, ovariectomized (OVX) and aged mice were used as osteoporotic models to test the effect of PCK2 on osteoporosis. The bone formation and adipocyte accumulation were assessed by micro-CT and histological analysis. The multipotent capacity of control and osteoporotic BMMSCs were evaluated by quantitative real time-polymerase chain reaction (qRT-PCR) and western blot analysis. ResultsPCK2 expression levels were significantly decreased in BMMSCs from OVX and aged mice. Furthermore, PCK2 could inhibit adipogenesis of BMMSCs and thus resisting lipid droplet formation and attenuating bone loss in osteoporotic mice. Mechanistically, we detected that autophagy level was decreased in BMMSCs of osteoporotic mice, while overexpression of PCK2 in vivo could rescued the autophagy activity. We further indicated that PCK2 could reverse osteopenia phenotype and adipose formation in OVX and aged mice partially via autophagy.ConclusionsCollectively, we suggested that PCK2 could attenuate bone loss and adipocyte accumulation of BMMSCs in osteoporotic mice through autophagy dependent manner. Our study indicated that PCK2 could be a brand and effective therapeutic target for osteoporosis treatment.

scholarly journals The mechanoresponse of bone is closely related to the osteocyte lacunocanalicular network architecture

2020 ◽  
Vol 117 (51) ◽  
pp. 32251-32259
Author(s):  
Alexander Franciscus van Tol ◽  
Victoria Schemenz ◽  
Wolfgang Wagermaier ◽  
Andreas Roschger ◽  
Hajar Razi ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Network Structure ◽  
Network Architecture ◽  
Local Strain ◽  
Bone Adaptation ◽  
Micro Computed Tomography ◽  
Entire Cross Section ◽  
Element Analysis ◽  
3D Network

Organisms rely on mechanosensing mechanisms to adapt to changes in their mechanical environment. Fluid-filled network structures not only ensure efficient transport but can also be employed for mechanosensation. The lacunocanalicular network (LCN) is a fluid-filled network structure, which pervades our bones and accommodates a cell network of osteocytes. For the mechanism of mechanosensation, it was hypothesized that load-induced fluid flow results in forces that can be sensed by the cells. We use a controlled in vivo loading experiment on murine tibiae to test this hypothesis, whereby the mechanoresponse was quantified experimentally by in vivo micro-computed tomography (µCT) in terms of formed and resorbed bone volume. By imaging the LCN using confocal microscopy in bone volumes covering the entire cross-section of mouse tibiae and by calculating the fluid flow in the three-dimensional (3D) network, we could perform a direct comparison between predictions based on fluid flow velocity and the experimentally measured mechanoresponse. While local strain distributions estimated by finite-element analysis incorrectly predicts preferred bone formation on the periosteal surface, we demonstrate that additional consideration of the LCN architecture not only corrects this erroneous bias in the prediction but also explains observed differences in the mechanosensitivity between the three investigated mice. We also identified the presence of vascular channels as an important mechanism to locally reduce fluid flow. Flow velocities increased for a convergent network structure where all of the flow is channeled into fewer canaliculi. We conclude that, besides mechanical loading, LCN architecture should be considered as a key determinant of bone adaptation.

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