Periosteal microcirculatory action of chronic estrogen supplementation in osteoporotic rats challenged with tourniquet ischemia

Transient ischemia of osteoporotic bones during elective orthopedic surgery or fracture repair carries risks for serious complications, and estrogen loss or replacement has a potential to influence ischemia–reperfusion-induced inflammatory activation. To clarify this, we investigated the periosteal...

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Veröffentlicht in:Life sciences (1973) 2011-01, Vol.88 (3), p.156-162
Hauptverfasser: Szabó, Andrea, Hartmann, Petra, Varga, Renata, Jánvári, Kristóf, Lendvai, Zsanett, Szalai, Irén, Gomez, Izabella, Varga, Gabriella, Greksa, Ferenc, Németh, István, Rázga, Zsolt, Keresztes, Margit, Garab, Dénes, Boros, Mihály
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container_end_page 162
container_issue 3
container_start_page 156
container_title Life sciences (1973)
container_volume 88
creator Szabó, Andrea
Hartmann, Petra
Varga, Renata
Jánvári, Kristóf
Lendvai, Zsanett
Szalai, Irén
Gomez, Izabella
Varga, Gabriella
Greksa, Ferenc
Németh, István
Rázga, Zsolt
Keresztes, Margit
Garab, Dénes
Boros, Mihály
description Transient ischemia of osteoporotic bones during elective orthopedic surgery or fracture repair carries risks for serious complications, and estrogen loss or replacement has a potential to influence ischemia–reperfusion-induced inflammatory activation. To clarify this, we investigated the periosteal inflammatory changes in a clinically relevant time frame in ovariectomized rats, an experimental model of postmenopausal bone loss. Furthermore, the effects of chronic estrogen supplementation on the postischemic local and systemic inflammatory reactions were assessed. Bilateral ovariectomy or sham operation was performed in 3-month-old female Sprague–Dawley rats. Five months later, estrogen replacement therapy with 17β-estradiol (20 μg − 1 kg − 1 day − 1 ) or vehicle treatment was initiated. The microcirculatory inflammatory consequences of 60-min total hindlimb ischemia followed by 180-min reperfusion were examined 11 months after ovariectomy and were compared with those in 3-month-old animals. The osteoporosis that developed 5 months after ovariectomy was significantly ameliorated by estrogen replacement therapy. Both in ovariectomized and in non-ovariectomized animals, ischemia–reperfusion elevated the neutrophil adherence ~ 3-fold in the postcapillary venules of the periosteum (intravital microscopy), with an ~ 50–60% increase in intravascular neutrophil activation (CD11b; FACS analysis), an enhanced TNF-α release (ELISA) and periosteal expression of ICAM-1 (the endothelial ligand of CD11b; immunohistochemistry). Exogenous 17β-estradiol considerably reduced TNF-α release and the number of neutrophil–endothelial interactions in the periosteum, without affecting the CD11b and ICAM-1 expression changes. Osteoporosis itself does not increase the magnitude of the limb ischemia–reperfusion-associated periosteal inflammatory reaction. Chronic estrogen supplementation, however, reverses osteoporosis and significantly ameliorates the microcirculatory consequences of transient ischemia.
doi_str_mv 10.1016/j.lfs.2010.11.004
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To clarify this, we investigated the periosteal inflammatory changes in a clinically relevant time frame in ovariectomized rats, an experimental model of postmenopausal bone loss. Furthermore, the effects of chronic estrogen supplementation on the postischemic local and systemic inflammatory reactions were assessed. Bilateral ovariectomy or sham operation was performed in 3-month-old female Sprague–Dawley rats. Five months later, estrogen replacement therapy with 17β-estradiol (20 μg − 1 kg − 1 day − 1 ) or vehicle treatment was initiated. The microcirculatory inflammatory consequences of 60-min total hindlimb ischemia followed by 180-min reperfusion were examined 11 months after ovariectomy and were compared with those in 3-month-old animals. The osteoporosis that developed 5 months after ovariectomy was significantly ameliorated by estrogen replacement therapy. 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Both in ovariectomized and in non-ovariectomized animals, ischemia–reperfusion elevated the neutrophil adherence ~ 3-fold in the postcapillary venules of the periosteum (intravital microscopy), with an ~ 50–60% increase in intravascular neutrophil activation (CD11b; FACS analysis), an enhanced TNF-α release (ELISA) and periosteal expression of ICAM-1 (the endothelial ligand of CD11b; immunohistochemistry). Exogenous 17β-estradiol considerably reduced TNF-α release and the number of neutrophil–endothelial interactions in the periosteum, without affecting the CD11b and ICAM-1 expression changes. Osteoporosis itself does not increase the magnitude of the limb ischemia–reperfusion-associated periosteal inflammatory reaction. Chronic estrogen supplementation, however, reverses osteoporosis and significantly ameliorates the microcirculatory consequences of transient ischemia.</description><subject>Analysis of Variance</subject><subject>Animals</subject><subject>bone resorption</subject><subject>CD11b Antigen - metabolism</subject><subject>Densitometry</subject><subject>enzyme-linked immunosorbent assay</subject><subject>estradiol</subject><subject>Estradiol - pharmacology</subject><subject>Estrogen Replacement Therapy</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Hindlimb - surgery</subject><subject>Image Processing, Computer-Assisted</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Intravital microscopy</subject><subject>ischemia</subject><subject>Ischemia - immunology</subject><subject>Ischemia - physiopathology</subject><subject>Ischemia–reperfusion</subject><subject>long term effects</subject><subject>Microcirculation - drug effects</subject><subject>Microcirculation - physiology</subject><subject>microscopy</subject><subject>Microscopy, Video</subject><subject>Neutrophil</subject><subject>neutrophils</subject><subject>Neutrophils - immunology</subject><subject>orthopedics</subject><subject>osteoporosis</subject><subject>Osteoporosis - immunology</subject><subject>Osteoporosis - physiopathology</subject><subject>Ovariectomy</subject><subject>periosteum</subject><subject>Periosteum - blood supply</subject><subject>postmenopause</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>risk</subject><subject>tumor necrosis factor-alpha</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2LFDEQxYMo7rj6B3jRvnnqsSrp9AeeZPELFhR0zyGTVGYydHfaJL2yJ_91M87qUQ9FUfB7j0c9xp4jbBGwfX3cji5tOZxu3AI0D9gG-26ooRX4kG0AeFMLDvKCPUnpCABSduIxu-AILW8FbNjPLxR9SJn0WE3exGB8NOuoc4h3lTbZh7kKrjKHGGZvKko5hj3NVVqXZaSJ5qx_M75gxSUsIYZcwKhzKio9jjTvyVY_fD5UOaxx9t9XypVP5kCT10_ZI6fHRM_u9yW7ef_u29XH-vrzh09Xb69r00Cfa0l253onuZG8abVF3GnBZTfYQfa8GziHQVrSTmJrdwN3wnRStNhY0NIRiUv26uy7xFACpKymEoHGUc8U1qT6thj1ouv-TwqJ2DXIC4lnsrwtpUhOLdFPOt4pBHUqSB1VKUidClKIqhRUNC_u3dfdRPav4k8jBXh5BpwOSu-jT-rma3GQUAbb4US8ORNU_nXrKapkPM2GrI9ksrLB_yPAL3n3rYY</recordid><startdate>20110117</startdate><enddate>20110117</enddate><creator>Szabó, Andrea</creator><creator>Hartmann, Petra</creator><creator>Varga, Renata</creator><creator>Jánvári, Kristóf</creator><creator>Lendvai, Zsanett</creator><creator>Szalai, Irén</creator><creator>Gomez, Izabella</creator><creator>Varga, Gabriella</creator><creator>Greksa, Ferenc</creator><creator>Németh, István</creator><creator>Rázga, Zsolt</creator><creator>Keresztes, Margit</creator><creator>Garab, Dénes</creator><creator>Boros, Mihály</creator><general>Elsevier Inc</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QP</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20110117</creationdate><title>Periosteal microcirculatory action of chronic estrogen supplementation in osteoporotic rats challenged with tourniquet ischemia</title><author>Szabó, Andrea ; Hartmann, Petra ; Varga, Renata ; Jánvári, Kristóf ; Lendvai, Zsanett ; Szalai, Irén ; Gomez, Izabella ; Varga, Gabriella ; Greksa, Ferenc ; Németh, István ; Rázga, Zsolt ; Keresztes, Margit ; Garab, Dénes ; Boros, Mihály</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-5edbf8f52c5246ad11ba32579d95827922095deaf516db92f3c753614d0a5fee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Analysis of Variance</topic><topic>Animals</topic><topic>bone resorption</topic><topic>CD11b Antigen - metabolism</topic><topic>Densitometry</topic><topic>enzyme-linked immunosorbent assay</topic><topic>estradiol</topic><topic>Estradiol - pharmacology</topic><topic>Estrogen Replacement Therapy</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Hindlimb - surgery</topic><topic>Image Processing, Computer-Assisted</topic><topic>Immunohistochemistry</topic><topic>Inflammation</topic><topic>Intravital microscopy</topic><topic>ischemia</topic><topic>Ischemia - immunology</topic><topic>Ischemia - physiopathology</topic><topic>Ischemia–reperfusion</topic><topic>long term effects</topic><topic>Microcirculation - drug effects</topic><topic>Microcirculation - physiology</topic><topic>microscopy</topic><topic>Microscopy, Video</topic><topic>Neutrophil</topic><topic>neutrophils</topic><topic>Neutrophils - immunology</topic><topic>orthopedics</topic><topic>osteoporosis</topic><topic>Osteoporosis - immunology</topic><topic>Osteoporosis - physiopathology</topic><topic>Ovariectomy</topic><topic>periosteum</topic><topic>Periosteum - blood supply</topic><topic>postmenopause</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>risk</topic><topic>tumor necrosis factor-alpha</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Szabó, Andrea</creatorcontrib><creatorcontrib>Hartmann, Petra</creatorcontrib><creatorcontrib>Varga, Renata</creatorcontrib><creatorcontrib>Jánvári, Kristóf</creatorcontrib><creatorcontrib>Lendvai, Zsanett</creatorcontrib><creatorcontrib>Szalai, Irén</creatorcontrib><creatorcontrib>Gomez, Izabella</creatorcontrib><creatorcontrib>Varga, Gabriella</creatorcontrib><creatorcontrib>Greksa, Ferenc</creatorcontrib><creatorcontrib>Németh, István</creatorcontrib><creatorcontrib>Rázga, Zsolt</creatorcontrib><creatorcontrib>Keresztes, Margit</creatorcontrib><creatorcontrib>Garab, Dénes</creatorcontrib><creatorcontrib>Boros, Mihály</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Calcium &amp; 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To clarify this, we investigated the periosteal inflammatory changes in a clinically relevant time frame in ovariectomized rats, an experimental model of postmenopausal bone loss. Furthermore, the effects of chronic estrogen supplementation on the postischemic local and systemic inflammatory reactions were assessed. Bilateral ovariectomy or sham operation was performed in 3-month-old female Sprague–Dawley rats. Five months later, estrogen replacement therapy with 17β-estradiol (20 μg − 1 kg − 1 day − 1 ) or vehicle treatment was initiated. The microcirculatory inflammatory consequences of 60-min total hindlimb ischemia followed by 180-min reperfusion were examined 11 months after ovariectomy and were compared with those in 3-month-old animals. The osteoporosis that developed 5 months after ovariectomy was significantly ameliorated by estrogen replacement therapy. Both in ovariectomized and in non-ovariectomized animals, ischemia–reperfusion elevated the neutrophil adherence ~ 3-fold in the postcapillary venules of the periosteum (intravital microscopy), with an ~ 50–60% increase in intravascular neutrophil activation (CD11b; FACS analysis), an enhanced TNF-α release (ELISA) and periosteal expression of ICAM-1 (the endothelial ligand of CD11b; immunohistochemistry). Exogenous 17β-estradiol considerably reduced TNF-α release and the number of neutrophil–endothelial interactions in the periosteum, without affecting the CD11b and ICAM-1 expression changes. Osteoporosis itself does not increase the magnitude of the limb ischemia–reperfusion-associated periosteal inflammatory reaction. Chronic estrogen supplementation, however, reverses osteoporosis and significantly ameliorates the microcirculatory consequences of transient ischemia.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>21062630</pmid><doi>10.1016/j.lfs.2010.11.004</doi><tpages>7</tpages></addata></record>
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subjects Analysis of Variance
Animals
bone resorption
CD11b Antigen - metabolism
Densitometry
enzyme-linked immunosorbent assay
estradiol
Estradiol - pharmacology
Estrogen Replacement Therapy
Female
Flow Cytometry
Hindlimb - surgery
Image Processing, Computer-Assisted
Immunohistochemistry
Inflammation
Intravital microscopy
ischemia
Ischemia - immunology
Ischemia - physiopathology
Ischemia–reperfusion
long term effects
Microcirculation - drug effects
Microcirculation - physiology
microscopy
Microscopy, Video
Neutrophil
neutrophils
Neutrophils - immunology
orthopedics
osteoporosis
Osteoporosis - immunology
Osteoporosis - physiopathology
Ovariectomy
periosteum
Periosteum - blood supply
postmenopause
Rats
Rats, Sprague-Dawley
risk
tumor necrosis factor-alpha
Tumor Necrosis Factor-alpha - metabolism
title Periosteal microcirculatory action of chronic estrogen supplementation in osteoporotic rats challenged with tourniquet ischemia
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