Protection against glucocorticoid-induced damage in human tenocytes by modulation of ERK, Akt, and forkhead signaling

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dc.contributor.author Poulsen, Raewyn en
dc.contributor.author Carr, AJ en
dc.contributor.author Hulley, PA en
dc.date.accessioned 2016-07-22T02:12:31Z en
dc.date.available 2010-11-22 en
dc.date.issued 2011-02 en
dc.identifier.citation Endocrinology, 2011, 152 (2), pp. 503 - 514 en
dc.identifier.issn 0013-7227 en
dc.identifier.uri http://hdl.handle.net/2292/29548 en
dc.description.abstract Antiinflammatory glucocorticoid (GC) injections are extensively used to treat painful tendons. However, GC cause severe tissue wasting in other collagen-producing tissues such as skin and bone. The objective of this study was to determine the effects of GC on tenocytes and to explore strategies to protect against unwanted side effects of GC treatment. Cell survival, collagen production, and the induction of signaling pathways in primary human tenocytes treated with dexamethasone (Dex) were assessed. Antioxidant and growth factor approaches to protection were tested. Dex treatment resulted in reduced viable cell number, cell proliferation, and collagen production. Dex induced reactive oxygen species generation in tenocytes and strongly up-regulated the stress-response transcription factors FOXO1 and FOXO3A. Phosphorylation of ERK and protein kinase B/Akt, which regulate cell proliferation and also inhibit forkhead activity, was decreased. Chemical inhibition of ERK or Akt activity significantly reduced tenocyte cell number. Ameliorating the Dex-induced reduction in ERK or Akt activity by cotreatment with vitamin C or insulin protected against the Dex-induced reduction in cell number. Silencing FOXO1 prevented the Dex-induced reduction in collagen 1α1 expression. Cotreatment with vitamin C or insulin protected against the Dex-induced increase in FOXO and the Dex-induced inhibition of collagen 1α1 expression. Reduced ERK and Akt activation and increased forkhead signaling contribute to the negative effects of GC on tenocytes. Cotreatment therapies that target these signaling pathways are protective. Vitamin C in particular may be a clinically useable co-therapy to reduce connective tissue side effects associated with GC therapy. en
dc.description.uri http://www.ncbi.nlm.nih.gov/pubmed/21209015 en
dc.format.medium Print-Electronic en
dc.language English en
dc.relation.ispartofseries Endocrinology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0013-7227/ http://press.endocrine.org/page/authors en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.subject Cells, Cultured en
dc.subject Humans en
dc.subject Reactive Oxygen Species en
dc.subject Ascorbic Acid en
dc.subject Dexamethasone en
dc.subject Collagen en
dc.subject Insulin en
dc.subject Extracellular Signal-Regulated MAP Kinases en
dc.subject Glycosaminoglycans en
dc.subject RNA, Small Interfering en
dc.subject Anti-Inflammatory Agents en
dc.subject Glucocorticoids en
dc.subject Blotting, Western en
dc.subject Immunohistochemistry en
dc.subject Reverse Transcriptase Polymerase Chain Reaction en
dc.subject Signal Transduction en
dc.subject Apoptosis en
dc.subject Cell Proliferation en
dc.subject Cell Survival en
dc.subject Phosphorylation en
dc.subject Adult en
dc.subject Middle Aged en
dc.subject Female en
dc.subject Male en
dc.subject Proto-Oncogene Proteins c-akt en
dc.subject Forkhead Transcription Factors en
dc.title Protection against glucocorticoid-induced damage in human tenocytes by modulation of ERK, Akt, and forkhead signaling en
dc.type Journal Article en
dc.identifier.doi 10.1210/en.2010-1087 en
pubs.issue 2 en
pubs.begin-page 503 en
pubs.volume 152 en
dc.description.version VoR - Version of Record en
dc.identifier.pmid 21209015 en
pubs.author-url http://press.endocrine.org/doi/abs/10.1210/en.2010-1087 en
pubs.end-page 514 en
pubs.publication-status Published en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 496435 en
pubs.org-id Medical and Health Sciences en
pubs.org-id School of Medicine en
pubs.org-id Medicine Department en
dc.identifier.eissn 1945-7170 en
pubs.record-created-at-source-date 2016-07-22 en
pubs.online-publication-date 2011-01-05 en
pubs.dimensions-id 21209015 en


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