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Microfluidic Enhancement of Intramedullary Pressure Increases Interstitial Fluid Flow and Inhibits Bone Loss in Hindlimb Suspended Mice
Authors
Aguirre
Bergula
+57Β more
Brighton
Bryant
Caulkins
Chen
Chen
Colleran
De Souza
Djien Tan
Dodd
Downey
Genetos
Gross
Gurkan
Hillsley
Jiang
Johnson
Kelly
Knothe Tate
Knothe Tate
Liu
Malone
Malone
McAllister
Nagatomi
Nagatomi
Nagatomi
Owan
Parfitt
Pavalko
Piekarski
Qin
Qin
Qin
Reich
Reich
Robling
Robling
Robling
Roelofsen
Skedros
Stevens
Stevens
Su
Sugiyama
Takai
Tu
Turner
Vezeridis
Wang
Warden
Weinbaum
You
You
You
You
Zhang
Zhou
Publication date
Publisher
Wiley Subscription Services, Inc., A Wiley Company
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on
PubMed
Abstract
Interstitial fluid flow (IFF) has been widely hypothesized to mediate skeletal adaptation to mechanical loading. Although a large body of in vitro evidence has demonstrated that fluid flow stimulates osteogenic and antiresorptive responses in bone cells, there is much less in vivo evidence that IFF mediates loading-induced skeletal adaptation. This is due in large part to the challenges associated with decoupling IFF from matrix strain. In this study we describe a novel microfluidic system for generating dynamic intramedullary pressure (ImP) and IFF within the femurs of alert mice. By quantifying fluorescence recovery after photobleaching (FRAP) within individual lacunae, we show that microfluidic generation of dynamic ImP significantly increases IFF within the lacunocanalicular system. In addition, we demonstrate that dynamic pressure loading of the intramedullary compartment for 3 minutes per day significantly eliminates losses in trabecular and cortical bone mineral density in hindlimb suspended mice, enhances trabecular and cortical structural integrity, and increases endosteal bone formation rate. Unlike previously developed modalities for enhancing IFF in vivo, this is the first model that allows direct and dynamic modulation of ImP and skeletal IFF within mice. Given the large number of genetic tools for manipulating the mouse genome, this model is expected to serve as a powerful investigative tool in elucidating the role of IFF in skeletal adaptation to mechanical loading and molecular mechanisms mediating this process. Β© 2010 American Society for Bone and Mineral Research
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Last time updated on 03/01/2020