Document Detail

Pressure gradients and transport in the murine femur upon hindlimb suspension.
MedLine Citation:
PMID:  16677866     Owner:  NLM     Status:  MEDLINE    
Interstitial fluid flow (IFF) is important in a number of processes, including stimulation of cells and nutrient and waste transport. In bone, it arises from the vascular pressure gradient between the medullary cavity and the lymphatic drainage at the periosteal surface and is enhanced by mechanical loading events. However, little is known about the pressure gradients experienced by bone cells in vivo and the role of the induced IFF in bone adaptation. This study investigated IFF changes in bone, in a disuse model and in ambulatory mice, from pressure gradients measured by telemetry, and by fluorescent tracers. The role of IFF-mediated transport of oxygen was assessed by the levels of hypoxic osteocytes in mouse femur after disuse by hindlimb suspension and with or without femoral vein ligation. Femoral intramedullary pressures in alert mice decreased to 77% upon hindlimb suspension and increased by 25% upon ligation, relative to baseline. To determine relative perfusion of cortical bone by IFF, the localization of intracardiac-injected fluorescent albumin conjugate with osteocytes was monitored. The number of osteocytic lacunae per bone area positive for Texas Red albumin was increased by 31% within 20-40 s, in the ligated femur compared to the contralateral sham femur. This confirmed that interstitial fluid flow was increased by femoral vein ligation and indicated that the increase was proportional to the pressure increase. Unloaded bone osteocytes were not hypoxic when compared to loaded controls and venous ligation did not alter these levels significantly. These results support the hypothesis that disuse by hindlimb suspension leads to decreased pressure gradients, which indicate lower IFF. Similarly, the increased pressure gradients, seen upon venous ligation, increased IFF from marrow to periosteum. While a decrease in intramedullary pressure in disuse suggests a decrease in IFF, this did not lead to hypoxia in osteocytes. We conclude that decreased oxygen convective transport in the mouse hindlimb disuse model does not account for cortical bone loss. This study is important in increasing our understanding of the mechanotransductory pathways involved in bone loading and unloading.
H Y Stevens; D R Meays; J A Frangos
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-05-03
Journal Detail:
Title:  Bone     Volume:  39     ISSN:  8756-3282     ISO Abbreviation:  Bone     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-07     Completed Date:  2006-09-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8504048     Medline TA:  Bone     Country:  United States    
Other Details:
Languages:  eng     Pagination:  565-72     Citation Subset:  IM    
La Jolla Bioengineering Institute, 505 Coast Boulevard South, La Jolla, CA 92037, USA.
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MeSH Terms
Femur* / cytology,  metabolism
Hindlimb Suspension
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Mice, Inbred C57BL
Grant Support
Reg. No./Substance:
0/Hif1a protein, mouse; 0/Hypoxia-Inducible Factor 1, alpha Subunit

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