Does bone perfusion/reperfusion initiate bone remodeling and the stress fracture syndrome?

Otter, Mark W.; Qin, Yi‐Xian; Rubin, Clinton T.; McLeod, Kenneth J.

doi:10.1054/mehy.1998.0782

Cited by 48 publications

(28 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previously, we and others have shown that runx2 and alkaline phosphatase (AP) expression (markers of osteoblast lineage selection and differentiation, respectively) are markedly suppressed in osteoblasts under hypoxic conditions Ontiveros et al, 2004;Salim et al, 2004]. These findings correspond with reports demonstrating that conditions of decreased bone oxygenation such as decreased arterial supply (chronic intramedullary pressure [Kiaer et al, 1992;Otter et al, 1999]) and inflammation (osteoarthritis [Kofoed, 1986;Kiaer et al, 1988]) are associated with bone loss. For example, ligation of bone nutrient arteries, lower extremity arterial disease and chronic pulmonary disease lead to decreased bone pO 2 and correspondingly bone loss in affected limbs [Kiaer et al, 1992;Vogt et al, 1997;Harrison et al, 2002;Szymanski et al, 2002;Ionescu and Schoon, 2003].…”

supporting

confidence: 83%

See 1 more Smart Citation

Prolyl‐hydroxylase inhibition and HIF activation in osteoblasts promotes an adipocytic phenotype

Irwin

LaPres

Kinser

et al. 2006

J of Cellular Biochemistry

View full text Add to dashboard Cite

Bone is a dynamic environment where cells sense and adapt to changes in nutrient and oxygen availability. Conditions associated with hypoxia in bone are also associated with bone loss. In vitro hypoxia (2% oxygen) alters gene expression in osteoblasts and osteocytes and induces cellular changes including the upregulation of hypoxia inducible factor (HIF) levels. Our studies show that osteoblasts respond to hypoxia (2% oxygen) by enhancing expression of genes associated with adipocyte/lipogenesis phenotype (C/EBPbeta, PPARgamma2, and aP2) and by suppressing expression of genes associated with osteoblast differentiation (alkaline phosphatase, AP). Hypoxia increased HIF protein levels, hypoxic response element (HRE) binding, and HRE-reporter activity. We also demonstrate that prolyl-hydroxylases 2 and 3 (PHD2, PHD3), one of the major factors coordinating HIF degradation under normoxic but not hypoxic conditions, are induced in osteoblasts under hypoxic conditions. To further determine the contribution of PHDs and upregulated HIF activity in modulating osteoblast phenotype, we treated osteoblasts with a PHD inhibitor, dimethyloxaloylglycine (DMOG), and maintained cells under normoxic conditions. Similar to hypoxic conditions, HRE reporter activity was increased and adipogenic gene expression was increased while osteoblastic genes were suppressed. Taken together, our findings indicate a role for PHDs and HIFs in the regulation of osteoblast phenotype.

show abstract

supporting

confidence: 83%

“…Bone is a dynamic environment that exhibits cell sensing, metabolic adaptation, and changes in oxygen availability [Kofoed, 1986;Kiaer et al, 1988Kiaer et al, , 1992Otter et al, 1999;Harrison et al, 2002;Szymanski et al, 2002;Ionescu and Schoon, 2003]. Osteoblasts are one of the cell types in bone that are capable of responding to hypoxia.…”

mentioning

confidence: 99%

Prolyl‐hydroxylase inhibition and HIF activation in osteoblasts promotes an adipocytic phenotype

Irwin

LaPres

Kinser

et al. 2006

J of Cellular Biochemistry

View full text Add to dashboard Cite

show abstract

“…The blood supply via the marrow is primarily, but not entirely, centrifugal (Brookes, 1967;Singh and Brookes, 1971;Slater et al, 1991;Churchill et al, 1992;Kiaer, 1994;Bridgeman and Brookes, 1996). The marrow pressure caused solely by the circulation is on the order of 10 to SOmmHg, depending on the species (Kumar et al, 1979;Bryant, 1983;Otter et al, 1999), and is approximately ISmmHg in the turkey ulna. While mechanical fading can increase marrow pressure on the order of 1 SOmmHg with 800~ 1000 microstrain axial loading, ImP oscillations which can attain pressures of 60mmHg, would incorporate with the circulatory blood pressure and impact on bone fluid flow.…”

Section: Discussionmentioning

confidence: 99%

“…Second, a nutrient pathway for metabolism and the proper disposal of waste products generated from catabolic activities occur through fluid channels. In the soft tissue, molecular diffusion is considered the major pathway for transportation of metabolites (Otter et al, 1999). Because of the relatively dense structure of cortical bone, however, the diffusive mechanism may, in fact, be insufficient to play an adequate role in transporting metabolic constituents between osteocytes and the surrounding vascular canals.…”

Section: Discussionmentioning

confidence: 99%

Stress Fracture Etiology as Dependent on Mechanically Induced Fluid Flow

Qin¹

2003

View full text Add to dashboard Cite

Public reporting burden for this collection of information is estinaated to average 1 hour per response, including the time for reviewing instmctions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway. Suite 1204, Artington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0168), Washington, DC 20503 AGENCY USE ONLY (Leave blank) REPORT DATE March 2003 REPORT TYPE AND DATES COVEREDAnnual (1 Mar 2002 -28 Feb 2003 TITLE AND SUBTITLE Stress Fracture Etiology as Dependent on Mechanically Induced Fluid Flow AUTHOR(S)Yi-Xian Qin, Ph.D. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)State University of New York Research Foundation Stony Brook, New York 11794-3362 E-Mail: Yi-Xian.Qin@sunysb.edu SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES)U SUPPLEMENTARY NOTESOriginal contains color plates: All DTIC reproductions will be in black and white. 12a. DISTRIBUTION/AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited 12b. DISTRIBUTION CODE ABSTRACT (Maximum 200 Words)Bone fluid flow is hypothesized to initiate aberrant remodeling which can ultimately compromise bone quantity and quality. Thus, pathologic response of load-induced fluid flow can potentially damage tissue viability, and initiate bone's remodeling process, ultimately leading to the stress fracture syndrome. The research goal is evaluated through two primary specific aims: (1) repetitive fluid flow, as dependent on magnitude and duration, will stimulate pathological remodeling; and (2) cyclic intramedullary pressure (ImP) will induce nutrient vessel remodeling and constriction, and thus partially reduce nutritional flow to the cortex. Results have shown that within the physiological range, bone formation is proportional to applied fluid flow stimulation. While the pressure exceeds the physiological intensity of falls within the pathologic range, i.e., addition to normal physical loading, it triggers extensive remodeling and thus even weaken the quality of bone, i.e., increase intracortical porosity and induce lesions. Repetitive cyclic fluid flow in bone has shown an effect on the nutrient vessel remodeling inducing vessel wall thickening, which may potentially contribute to pathological remodeling in bone. These results may provide insight of fluid flow in physiological and pathological remodeling and its role in stress fracture. SUBJECT TERMSNo Subject Terms Provided. SECURITY CLASSIFICA TION OF REPORT A. IntroductionMusculoskeletal complications tiiat arise in tine training of recmlts represent a critical health problem for the military. Stress fractures almost exclusively occur in physically active individuals, e.g., dancers, joggers, and ...

show abstract

“…Capillary filtration, muscle pump and bone fluid flow illaries in the medullary canal-a classical Starling resister effect-resulting in both medullary and cortical ischemia (Otter et al, 1999). However, long periods of high IMP seem to occur only under pathological conditions such as ischemic osteonecrosis (Ficat and Arlet, 1980) and bone marrow edema syndrome (Jones, 1997).…”

Section: H Winetmentioning

confidence: 99%

A bone fluid flow hypothesis for muscle pump-driven capillary filtration: ii proposed role for exercise in erodible scaffold implant incorporation

Winet

2003

eCM

View full text Add to dashboard Cite

A model is presented for enhancement of fluid flow through bone matrix and any porous tissue engineering scaffold implanted within it. The mechanism of enhancement is the skeletal muscle pump in compartments adjacent to the bone. Pressure waves from muscle pump contractions aided by increased blood pressure during exercise coupled with temporary occlusion of arteries leading to and veins from the bone, increase hydraulic pressure in cortical bone capillaries so as to amplify capillary filtration. It is proposed that capillary filtration increase is sufficiently convective to contribute to bone fluid flow and associated percolation through tissue engineered scaffold matrix implants. Importance of this contribution is its relative role in maintaining seeded cells in bioreactor scaffolds. Validation of the hypothesis starts at a minimum level of demonstrating that capillary filtration is convective. At a maximum level confirmation of the hypothesis requires demonstration that capillary filtration-based interstitial flow is sufficient to stimulate not only host bone cells (as proposed in part I of the hypothesis) but bioreactor-seeded cells as well. Preliminary data is presented supporting the prediction that skeletal muscle contraction generates convective capillary filtration.

show abstract

Does bone perfusion/reperfusion initiate bone remodeling and the stress fracture syndrome?

Cited by 48 publications

References 36 publications

Prolyl‐hydroxylase inhibition and HIF activation in osteoblasts promotes an adipocytic phenotype

Prolyl‐hydroxylase inhibition and HIF activation in osteoblasts promotes an adipocytic phenotype

Stress Fracture Etiology as Dependent on Mechanically Induced Fluid Flow

A bone fluid flow hypothesis for muscle pump-driven capillary filtration: ii proposed role for exercise in erodible scaffold implant incorporation

Contact Info

Product

Resources

About