| Hypoxia: a critical regulator of early human tendinopathy. | |
| | |
MedLine Citation:
|
PMID: 21972243 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
OBJECTIVES: To seek evidence for the role of hypoxia in early human tendinopathy, and thereafter to explore mechanisms whereby tissue hypoxia may regulate apoptosis, inflammatory mediator expression and matrix regulation in human tenocytes.METHODS: Fifteen torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of the subscapularis tendon were collected from 10 patients undergoing arthroscopic stabilisation surgery. Markers of hypoxia were quantified by immunohistochemical methods. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction. The impact of hypoxia upon tenocyte biology ex vivo was measured using quantitative real-time PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V fluorescence-activated cell sorter staining.RESULTS: Increased expression of hypoxia-inducible factor 1α, Bcl-2 and clusterin was detected in subscapularis tendon samples compared with both matched torn samples and non-matched control samples (p<0.01). Hypoxic tenocytes exhibited increased production of proinflammatory cytokines (p<0.001), altered matrix regulation (p<0.01) with increased production of collagen type III operating through a mitogen-activated protein kinase-dependent pathway. Finally, hypoxia increased the expression of several mediators of apoptosis and thereby promoted tenocyte apoptosis.CONCLUSION: Hypoxia promotes the expression of proinflammatory cytokines, key apoptotic mediators and drives matrix component synthesis towards a collagen type III profile by human tenocytes. The authors propose hypoxic cell injury as a critical pathophysiological mechanism in early tendinopathy offering novel therapeutic opportunities in the management of tendon disorders. |
| | |
Authors:
|
Neal L Millar; James H Reilly; Shauna C Kerr; Abigail L Campbell; Kevin J Little; William J Leach; Brian P Rooney; George A C Murrell; Iain B McInnes |
Related Documents
:
|
19734463 - Epithelial gm-csf induction by candida glabrata. 15368613 - Elevated concentration of cerebrospinal fluid tissue transglutaminase in parkinson's di... 19734463 - Epithelial gm-csf induction by candida glabrata. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-10-4 |
Journal Detail:
|
Title: Annals of the rheumatic diseases Volume: - ISSN: 1468-2060 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
|
Created Date: 2011-10-5 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0372355 Medline TA: Ann Rheum Dis Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
1Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Effectiveness of disease-modifying antirheumatic drug co-therapy with methotrexate and leflunomide i...
Next Document: Methylation of L1Hs promoters are lower on the inactive X, has a tendency of being higher on autosom...