| Oxygen tension regulates preosteocyte maturation and mineralization. | |
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MedLine Citation:
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PMID: 18485858 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Oxygen availability is a critical signal for proper development of many tissues, however there is limited knowledge of its role in the maturation of bone cells. To test the hypothesis that low pO2 regulates bone cell mineralization, MLO-A5 and MLO-Y4 cells were cultured in monolayer and three-dimensional alginate scaffolds in hypoxia (2% O2) or normoxia (20% O2). Hypoxia reduced mineralization and decreased alkaline phosphatase activity of preosteocyte-like MLO-A5 cells in both monolayer and alginate cultures. Similar changes in osteogenic activity were seen when the were subjected to chemical hypoxia. Likewise, Osteocyte-like MLO-Y4 cells also exhibited reduced osteogenic activity in hypoxia relative to normoxic controls. Based on these observations, it is concluded that a low pO2 decreased the mineralization potential of bone cells at both early and late stages of maturation. Since the oxemic state is transduced by the transcription factor, HIF-1alpha, experiments were performed to determine if this protein was responsible for the observed changes in mineral formation. It was noted that when HIF-1alpha was silenced, mineralization activities were not restored. Indeed, in hypoxia, in relationship to wild type controls, the mineralization potential of the knockdown cells was further reduced. Based on these findings, it is concluded that the osteogenic activity of preosteocyte-like cells is dependent on both the O2 tension and the expression of HIF-1alpha. |
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Authors:
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Adam M Zahm; Michael A Bucaro; Vickram Srinivas; Irving M Shapiro; Christopher S Adams |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-03-29 |
Journal Detail:
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Title: Bone Volume: 43 ISSN: 8756-3282 ISO Abbreviation: Bone Publication Date: 2008 Jul |
Date Detail:
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Created Date: 2008-06-16 Completed Date: 2008-08-15 Revised Date: 2011-02-04 |
Medline Journal Info:
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Nlm Unique ID: 8504048 Medline TA: Bone Country: United States |
Other Details:
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Languages: eng Pagination: 25-31 Citation Subset: IM |
Affiliation:
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Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA 19107, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alkaline Phosphatase
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metabolism Animals Blotting, Western Calcification, Physiologic* Cell Line Mice Osteocytes / cytology*, enzymology Oxygen / metabolism* RNA, Small Interfering Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
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AR-052273/AR/NIAMS NIH HHS; DE-016383/DE/NIDCR NIH HHS; DE-10875/DE/NIDCR NIH HHS; R01 AR051303-01A2/AR/NIAMS NIH HHS; R01 AR051303-02/AR/NIAMS NIH HHS; R01 AR051303-03/AR/NIAMS NIH HHS; R01 AR051303-03S1/AR/NIAMS NIH HHS; R01 DE010875-06/DE/NIDCR NIH HHS; R01 DE010875-07/DE/NIDCR NIH HHS; R01 DE010875-08/DE/NIDCR NIH HHS; R01 DE010875-09/DE/NIDCR NIH HHS; R01 DE010875-10/DE/NIDCR NIH HHS; R01 DE010875-11/DE/NIDCR NIH HHS; R01 DE010875-12/DE/NIDCR NIH HHS; R01 DE010875-12S1/DE/NIDCR NIH HHS; R01 DE010875-13/DE/NIDCR NIH HHS; R01 DE013319-01/DE/NIDCR NIH HHS; R01 DE013319-02/DE/NIDCR NIH HHS; R01 DE013319-03/DE/NIDCR NIH HHS; R01 DE013319-04/DE/NIDCR NIH HHS; R01 DE013319-05/DE/NIDCR NIH HHS; R01 DE013319-06/DE/NIDCR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Small Interfering; 7782-44-7/Oxygen; EC 3.1.3.1/Alkaline Phosphatase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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