Targeting the lateral but not the third ventricle induces bone loss in ewe: an experimental approach to generate an improved large animal model of osteoporosis
Osteoporosis is a chronic disease characterized by bone loss and increased skeletal fragility. Large animal models are required for preclinical testing of new therapeutic approaches. We have recently demonstrated that continuous intracerebroventricular (ICV) application of leptin into the lateral ve...
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| Veröffentlicht in: | The journal of trauma 2012-03, Vol.72 (3), p.720-726 |
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| creator | Oheim, Ralf Beil, Frank Timo Barvencik, Florian Egermann, Marcus Amling, Michael Clarke, Iain J Pogoda, Pia |
| description | Osteoporosis is a chronic disease characterized by bone loss and increased skeletal fragility. Large animal models are required for preclinical testing of new therapeutic approaches. We have recently demonstrated that continuous intracerebroventricular (ICV) application of leptin into the lateral ventricle (LV) induces bone loss in ewe. On the basis of these findings, we reasoned that the third ventricle (TV) is an even better target because of its closer location to the hypothalamus that mediates leptin effects on bone.
Corriedale sheep were randomly mixed to four groups of four ewe each: control entire (control), ovarectomy plus ICV application of cerebrospinal fluid (OVX), OVX plus ICV application of leptin into the LV (leptin-LV); and ICV application of leptin into the TV (leptin-TV). After 3 months, histomorphometric characterization and bone turnover parameters were analyzed.
Highly significant loss of trabecular bone was observed only in leptin-LV group. Increased osteoclast indices and urinary cross-lap excretion were observed in OVX and leptin-TV group. In contrast, serum parameters of osteoblast activity were only significantly decreased in leptin-LV group. Autopsy of ewe brain showed fibrosis around the stainless steel cannula in leptin-TV group.
ICV application of leptin into the LV strongly reduces bone formation and leads to a highly significant trabecular bone loss in ewe. In contrast, ICV application of leptin into the TV is technically more demanding and results are unpredictable, because the required use of stainless steel cannula induces peri-implant fibrosis that might prevent leptin to enter the cerebrospinal fluid. |
| doi_str_mv | 10.1097/TA.0b013e318238b3bd |
| format | Article |
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Corriedale sheep were randomly mixed to four groups of four ewe each: control entire (control), ovarectomy plus ICV application of cerebrospinal fluid (OVX), OVX plus ICV application of leptin into the LV (leptin-LV); and ICV application of leptin into the TV (leptin-TV). After 3 months, histomorphometric characterization and bone turnover parameters were analyzed.
Highly significant loss of trabecular bone was observed only in leptin-LV group. Increased osteoclast indices and urinary cross-lap excretion were observed in OVX and leptin-TV group. In contrast, serum parameters of osteoblast activity were only significantly decreased in leptin-LV group. Autopsy of ewe brain showed fibrosis around the stainless steel cannula in leptin-TV group.
ICV application of leptin into the LV strongly reduces bone formation and leads to a highly significant trabecular bone loss in ewe. In contrast, ICV application of leptin into the TV is technically more demanding and results are unpredictable, because the required use of stainless steel cannula induces peri-implant fibrosis that might prevent leptin to enter the cerebrospinal fluid.</description><identifier>ISSN: 0022-5282</identifier><identifier>EISSN: 2163-0763</identifier><identifier>DOI: 10.1097/TA.0b013e318238b3bd</identifier><identifier>PMID: 22491560</identifier><language>eng</language><publisher>United States</publisher><subject>Animal models ; Animals ; Autopsy ; Bone (trabecular) ; Bone loss ; Bone strength ; Bone turnover ; Brain ; Brain Diseases - chemically induced ; Brain Diseases - complications ; Brain Diseases - diagnosis ; Cerebrospinal fluid ; Disease Models, Animal ; Excretion ; Female ; Fibrosis ; Injections, Intraventricular ; Lateral Ventricles - abnormalities ; Lateral Ventricles - drug effects ; Leptin ; Leptin - administration & dosage ; Leptin - toxicity ; Osteoblasts ; Osteoblasts - drug effects ; Osteoblasts - metabolism ; Osteoclasts ; Osteogenesis ; Osteoporosis ; Osteoporosis - diagnosis ; Osteoporosis - etiology ; Osteoporosis - metabolism ; Ovariectomy ; Prognosis ; Sheep ; stainless steel ; Third Ventricle ; Trauma ; Ventricles (cerebral)</subject><ispartof>The journal of trauma, 2012-03, Vol.72 (3), p.720-726</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c288t-7f7811a633cbd277984304c9a4241fb8c09d65663e2b9076517b4b3d0851df8d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22491560$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oheim, Ralf</creatorcontrib><creatorcontrib>Beil, Frank Timo</creatorcontrib><creatorcontrib>Barvencik, Florian</creatorcontrib><creatorcontrib>Egermann, Marcus</creatorcontrib><creatorcontrib>Amling, Michael</creatorcontrib><creatorcontrib>Clarke, Iain J</creatorcontrib><creatorcontrib>Pogoda, Pia</creatorcontrib><title>Targeting the lateral but not the third ventricle induces bone loss in ewe: an experimental approach to generate an improved large animal model of osteoporosis</title><title>The journal of trauma</title><addtitle>J Trauma Acute Care Surg</addtitle><description>Osteoporosis is a chronic disease characterized by bone loss and increased skeletal fragility. Large animal models are required for preclinical testing of new therapeutic approaches. We have recently demonstrated that continuous intracerebroventricular (ICV) application of leptin into the lateral ventricle (LV) induces bone loss in ewe. On the basis of these findings, we reasoned that the third ventricle (TV) is an even better target because of its closer location to the hypothalamus that mediates leptin effects on bone.
Corriedale sheep were randomly mixed to four groups of four ewe each: control entire (control), ovarectomy plus ICV application of cerebrospinal fluid (OVX), OVX plus ICV application of leptin into the LV (leptin-LV); and ICV application of leptin into the TV (leptin-TV). After 3 months, histomorphometric characterization and bone turnover parameters were analyzed.
Highly significant loss of trabecular bone was observed only in leptin-LV group. Increased osteoclast indices and urinary cross-lap excretion were observed in OVX and leptin-TV group. In contrast, serum parameters of osteoblast activity were only significantly decreased in leptin-LV group. Autopsy of ewe brain showed fibrosis around the stainless steel cannula in leptin-TV group.
ICV application of leptin into the LV strongly reduces bone formation and leads to a highly significant trabecular bone loss in ewe. In contrast, ICV application of leptin into the TV is technically more demanding and results are unpredictable, because the required use of stainless steel cannula induces peri-implant fibrosis that might prevent leptin to enter the cerebrospinal fluid.</description><subject>Animal models</subject><subject>Animals</subject><subject>Autopsy</subject><subject>Bone (trabecular)</subject><subject>Bone loss</subject><subject>Bone strength</subject><subject>Bone turnover</subject><subject>Brain</subject><subject>Brain Diseases - chemically induced</subject><subject>Brain Diseases - complications</subject><subject>Brain Diseases - diagnosis</subject><subject>Cerebrospinal fluid</subject><subject>Disease Models, Animal</subject><subject>Excretion</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Injections, Intraventricular</subject><subject>Lateral Ventricles - abnormalities</subject><subject>Lateral Ventricles - drug effects</subject><subject>Leptin</subject><subject>Leptin - administration & dosage</subject><subject>Leptin - toxicity</subject><subject>Osteoblasts</subject><subject>Osteoblasts - drug effects</subject><subject>Osteoblasts - metabolism</subject><subject>Osteoclasts</subject><subject>Osteogenesis</subject><subject>Osteoporosis</subject><subject>Osteoporosis - diagnosis</subject><subject>Osteoporosis - etiology</subject><subject>Osteoporosis - metabolism</subject><subject>Ovariectomy</subject><subject>Prognosis</subject><subject>Sheep</subject><subject>stainless steel</subject><subject>Third Ventricle</subject><subject>Trauma</subject><subject>Ventricles (cerebral)</subject><issn>0022-5282</issn><issn>2163-0763</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkctq3TAQhkVpaQ5pnqBQtMzGiS6WLXd3CE0TCHRzuja6jM9RsS1XknN5mrxqJ02aRVbVZuDn-_8ZzRDymbMzzrr2fLc9Y5ZxCZJrIbWV1r8jG8EbWbG2ke_JhjEhKiW0OCInOf9i-FTTSaU-kiMh6o6rhm3I486kPZQw72k5AB1NgWRGatdC51j-auUQkqe3MJcU3Ag0zH51kKmNMxpizqhQuIOv1GC9XyCFCWFMMcuSonEHWiLdw4zJBZ6gMKF-Cx7bYXNUwoT0FD2MNA405gJxiSnmkD-RD4MZM5y81GPy8_Lb7uKquvnx_fpie1M5oXWp2qHVnJtGSme9aNtO15LVrjO1qPlgtWOdb1TTSBC2wwUp3traSs-04n7QXh6T0-dcnOz3Crn0U8gOxtHMENfc49JlrZju2H-gvOacMy0Rlc-ow8_kBEO_4HJMekDoKbLtd9v-7R3R9eWlwWon8K-ef1eTfwCC0pt5</recordid><startdate>201203</startdate><enddate>201203</enddate><creator>Oheim, Ralf</creator><creator>Beil, Frank Timo</creator><creator>Barvencik, Florian</creator><creator>Egermann, Marcus</creator><creator>Amling, Michael</creator><creator>Clarke, Iain J</creator><creator>Pogoda, Pia</creator><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></search><sort><creationdate>201203</creationdate><title>Targeting the lateral but not the third ventricle induces bone loss in ewe: an experimental approach to generate an improved large animal model of osteoporosis</title><author>Oheim, Ralf ; Beil, Frank Timo ; Barvencik, Florian ; Egermann, Marcus ; Amling, Michael ; Clarke, Iain J ; Pogoda, Pia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c288t-7f7811a633cbd277984304c9a4241fb8c09d65663e2b9076517b4b3d0851df8d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Autopsy</topic><topic>Bone (trabecular)</topic><topic>Bone loss</topic><topic>Bone strength</topic><topic>Bone turnover</topic><topic>Brain</topic><topic>Brain Diseases - chemically induced</topic><topic>Brain Diseases - complications</topic><topic>Brain Diseases - diagnosis</topic><topic>Cerebrospinal fluid</topic><topic>Disease Models, Animal</topic><topic>Excretion</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Injections, Intraventricular</topic><topic>Lateral Ventricles - abnormalities</topic><topic>Lateral Ventricles - drug effects</topic><topic>Leptin</topic><topic>Leptin - administration & dosage</topic><topic>Leptin - toxicity</topic><topic>Osteoblasts</topic><topic>Osteoblasts - drug effects</topic><topic>Osteoblasts - metabolism</topic><topic>Osteoclasts</topic><topic>Osteogenesis</topic><topic>Osteoporosis</topic><topic>Osteoporosis - diagnosis</topic><topic>Osteoporosis - etiology</topic><topic>Osteoporosis - metabolism</topic><topic>Ovariectomy</topic><topic>Prognosis</topic><topic>Sheep</topic><topic>stainless steel</topic><topic>Third Ventricle</topic><topic>Trauma</topic><topic>Ventricles (cerebral)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Oheim, Ralf</creatorcontrib><creatorcontrib>Beil, Frank Timo</creatorcontrib><creatorcontrib>Barvencik, Florian</creatorcontrib><creatorcontrib>Egermann, Marcus</creatorcontrib><creatorcontrib>Amling, Michael</creatorcontrib><creatorcontrib>Clarke, Iain J</creatorcontrib><creatorcontrib>Pogoda, Pia</creatorcontrib><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 & Calcified Tissue Abstracts</collection><jtitle>The journal of trauma</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Oheim, Ralf</au><au>Beil, Frank Timo</au><au>Barvencik, Florian</au><au>Egermann, Marcus</au><au>Amling, Michael</au><au>Clarke, Iain J</au><au>Pogoda, Pia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Targeting the lateral but not the third ventricle induces bone loss in ewe: an experimental approach to generate an improved large animal model of osteoporosis</atitle><jtitle>The journal of trauma</jtitle><addtitle>J Trauma Acute Care Surg</addtitle><date>2012-03</date><risdate>2012</risdate><volume>72</volume><issue>3</issue><spage>720</spage><epage>726</epage><pages>720-726</pages><issn>0022-5282</issn><eissn>2163-0763</eissn><abstract>Osteoporosis is a chronic disease characterized by bone loss and increased skeletal fragility. Large animal models are required for preclinical testing of new therapeutic approaches. We have recently demonstrated that continuous intracerebroventricular (ICV) application of leptin into the lateral ventricle (LV) induces bone loss in ewe. On the basis of these findings, we reasoned that the third ventricle (TV) is an even better target because of its closer location to the hypothalamus that mediates leptin effects on bone.
Corriedale sheep were randomly mixed to four groups of four ewe each: control entire (control), ovarectomy plus ICV application of cerebrospinal fluid (OVX), OVX plus ICV application of leptin into the LV (leptin-LV); and ICV application of leptin into the TV (leptin-TV). After 3 months, histomorphometric characterization and bone turnover parameters were analyzed.
Highly significant loss of trabecular bone was observed only in leptin-LV group. Increased osteoclast indices and urinary cross-lap excretion were observed in OVX and leptin-TV group. In contrast, serum parameters of osteoblast activity were only significantly decreased in leptin-LV group. Autopsy of ewe brain showed fibrosis around the stainless steel cannula in leptin-TV group.
ICV application of leptin into the LV strongly reduces bone formation and leads to a highly significant trabecular bone loss in ewe. In contrast, ICV application of leptin into the TV is technically more demanding and results are unpredictable, because the required use of stainless steel cannula induces peri-implant fibrosis that might prevent leptin to enter the cerebrospinal fluid.</abstract><cop>United States</cop><pmid>22491560</pmid><doi>10.1097/TA.0b013e318238b3bd</doi><tpages>7</tpages></addata></record> |
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| issn | 0022-5282 2163-0763 |
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| subjects | Animal models Animals Autopsy Bone (trabecular) Bone loss Bone strength Bone turnover Brain Brain Diseases - chemically induced Brain Diseases - complications Brain Diseases - diagnosis Cerebrospinal fluid Disease Models, Animal Excretion Female Fibrosis Injections, Intraventricular Lateral Ventricles - abnormalities Lateral Ventricles - drug effects Leptin Leptin - administration & dosage Leptin - toxicity Osteoblasts Osteoblasts - drug effects Osteoblasts - metabolism Osteoclasts Osteogenesis Osteoporosis Osteoporosis - diagnosis Osteoporosis - etiology Osteoporosis - metabolism Ovariectomy Prognosis Sheep stainless steel Third Ventricle Trauma Ventricles (cerebral) |
| title | Targeting the lateral but not the third ventricle induces bone loss in ewe: an experimental approach to generate an improved large animal model of osteoporosis |
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