uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Growth Factor and Protease Expression during Different Phases of Healing after Rabbit Deep Flexor Tendon Repair
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, Canada.
McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, Canada.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
2011 (English)In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 29, no 6, 886-892 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of the study was to contribute to the mapping of molecular events during flexor tendon healing, in particular the growth factors insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), matrix metalloproteinases (MMP-3 and MMP-13) and their inhibitors (tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-3, and the protease cathepsin K. In a rabbit model of flexor tendon injury, the mRNA expression for the growth factors, MMPs and TIMPs were measured in tendon and tendon sheath tissue at several time points (3, 6, 21, and 42 days) representing different phases of the healing process. We found that MMP-13 remained increased during the study period, whereas MMP-3 returned to normal levels within the first week after injury. TIMP-3 was down-regulated in the tendon sheaths. Cathepsin K was up-regulated in tendons and sheaths after injury. NGF was present in both tendons and sheaths, but unaltered. IGF-1 exhibited a late increase in the tendons, while VEGF was down-regulated at the later time points. In conclusion, we have demonstrated the presence of NGF in flexor tendons. MMP-13 expression appears to play a more protracted role in flexor tendon healing than MMP-3. The relatively low levels of endogenous IGF-1 and VEGF mRNA following injury support their potential beneficial role as exogenous modulators to optimize tendon healing and strength without increasing adhesion formation.

Place, publisher, year, edition, pages
2011. Vol. 29, no 6, 886-892 p.
Keyword [en]
tendon healing, VEGF, IGF-1, NGF, MMP, TIMP
National Category
Surgery
Research subject
Orthopaedics
Identifiers
URN: urn:nbn:se:uu:diva-120515DOI: 10.1002/jor.21330ISI: 000290360300015PubMedID: 21246620OAI: oai:DiVA.org:uu-120515DiVA: diva2:303474
Projects
Biomolecular aspects of flexor tendon healing
Available from: 2010-03-12 Created: 2010-03-12 Last updated: 2011-05-23Bibliographically approved
In thesis
1. Biomolecular Aspects of Flexor Tendon Healing
Open this publication in new window or tab >>Biomolecular Aspects of Flexor Tendon Healing
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Flexor tendon injuries in zone II of the hand (i.e. between the distal volar crease and the distal interphalangeal joint) can be costly for both the afflicted individual and society because of the high cost of a long rehabilitation period, complicated by tendon ruptures or scarring with adhesion formation, causing impaired range of motion. The aim of the present thesis was to characterize more fully the deep flexor tendon, the tendon sheath and their response to injury in a rabbit model in order to find potential targets to improve the outcome of repair.

The intrasynovial rabbit deep flexor tendon differed from the extrasynovial peroneus tendon in the expression of collagens and transforming growth factor-β1 gene expression. Differences were also found in collagen III and proteoglycans between regions of the flexor tendon subjected to either compressive or tensile load.

After laceration and subsequent repair of the flexor tendon, a shift in collagen gene expression from type I to type III occurred. Proteoglycans were generally increased with the notable exception of decorin, a potential inhibitor of the profibrotic transforming growth factor-β1 which was markedly increased during the first two weeks after repair in tendon tissue but remained unaltered in the sheaths. Both vascular endothelial growth factor and basic fibroblast growth factor mRNA levels remained essentially unaltered, whereas insulin-like growth factor-1 increased later in the healing process, suggesting potential beneficial effects of exogenous addition, increasing tendon strength through stimulating tenocyte proliferation and collagen synthesis.

Matrix metalloproteinase-13 mRNA levels increased and remained high in both tendon and sheath, whereas there was only a transient increase of matrix metalloproteinase-3 mRNA in tendon. We could also demonstrate a significant increase of the proportion of myofibroblasts, mast cells and neuropeptide containing nerve fibers in the healing tendon tissue, all components of the profibrotic myofibroblast-mast cell-neuropeptide pathway.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 59 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 544
Keyword
Flexor tendon healing, Growth factor, Metalloproteinase, Collagen, Proteoglycan, Myofibroblast, Hyaluronan synthase, Mast cell
National Category
Surgery
Research subject
Orthopaedics
Identifiers
urn:nbn:se:uu:diva-120304 (URN)978-91-554-7762-2 (ISBN)
Public defence
2010-05-06, Robergsalen, Ing. 40, Akademiska sjukhuset, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Projects
Biomolecular aspects of flexor tendon healing
Available from: 2010-04-15 Created: 2010-03-11 Last updated: 2010-04-16

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Berglund, Maria

Search in DiVA

By author/editor
Berglund, Maria
By organisation
Hand Surgery
In the same journal
Journal of Orthopaedic Research
Surgery

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 379 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf