| Fas receptor is required for estrogen deficiency-induced bone loss in mice. | |
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MedLine Citation:
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PMID: 20084056 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bone mass is determined by bone cell differentiation, activity, and death, which mainly occur through apoptosis. Apoptosis can be triggered by death receptor Fas (CD95), expressed on osteoblasts and osteoclasts and may be regulated by estrogen. We have previously shown that signaling through Fas inhibits osteoblast differentiation. In this study we analyzed Fas as a possible mediator of bone loss induced by estrogen withdrawal. At 4 weeks after ovariectomy (OVX), Fas gene expression was greater in osteoblasts and lower in osteoclasts in ovariectomized C57BL/6J (wild type (wt)) mice compared with sham-operated animals. OVX was unable to induce bone loss in mice with a gene knockout for Fas (Fas -/- mice). The number of osteoclasts increased in wt mice after OVX, whereas it remained unchanged in Fas -/- mice. OVX induced greater stimulation of osteoblastogenesis in Fas -/- than in wt mice, with higher expression of osteoblast-specific genes. Direct effects on bone cell differentiation and apoptosis in vivo were confirmed in vitro, in which addition of estradiol decreased Fas expression and partially abrogated the apoptotic and differentiation-inhibitory effect of Fas in osteoblast lineage cells, while having no effect on Fas-induced apoptosis in osteoclast lineage cells. In conclusion, the Fas receptor has an important role in the pathogenesis of postmenopausal osteoporosis by mediating apoptosis and inhibiting differentiation of osteoblast lineage cells. Modulation of Fas effects on bone cells may be used as a therapeutic target in the treatment of osteoresorptive disorders. |
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Authors:
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Natasa Kovacic; Danka Grcevic; Vedran Katavic; Ivan Kresimir Lukic; Vladimir Grubisic; Karlo Mihovilovic; Hrvoje Cvija; Peter Ian Croucher; Ana Marusic |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-18 |
Journal Detail:
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Title: Laboratory investigation; a journal of technical methods and pathology Volume: 90 ISSN: 1530-0307 ISO Abbreviation: Lab. Invest. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-25 Completed Date: 2010-03-23 Revised Date: 2010-09-02 |
Medline Journal Info:
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Nlm Unique ID: 0376617 Medline TA: Lab Invest Country: United States |
Other Details:
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Languages: eng Pagination: 402-13 Citation Subset: IM |
Affiliation:
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Department of Anatomy, University of Zagreb, School of Medicine, Zagreb, Croatia. natasa@mef.hr |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD95 / metabolism* Apoptosis Cell Differentiation* Cell Lineage Cells, Cultured Estrogens / deficiency* Fas Ligand Protein / metabolism Female Mice Mice, Inbred C57BL Mice, Knockout Osteoblasts / cytology*, physiology Osteoclasts / cytology*, physiology Osteoporosis / metabolism* Ovariectomy Signal Transduction |
| Grant Support | |
ID/Acronym/Agency:
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073828//Wellcome Trust; CRIGS 073828/Z/03/Z//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD95; 0/Estrogens; 0/Fas Ligand Protein; 0/Fas protein, mouse |
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