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Patterns of mRNA expression for matrix molecules and growth factors in flexor tendon injury: differences in the regulation between tendon and tendon sheath
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
McCaig Centre for Joint Injury and Artrhitis Research, University of Calgary, Calgary, Canada.
McCaig Centre for Joint Injury and Arthritis Research, University of Calgary, Calgary, Canada.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
2006 (English)In: Journal of Hand Surgery-American Volume, ISSN 0363-5023, E-ISSN 1531-6564, Vol. 31A, no 8, 1279-1287 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Injuries to tendons, particularly flexor tendons, can lead to loss of function after healing due to adhesion formation and other complications. The aim of this study was to increase our understanding of the healing process in tendons and tendon sheaths to develop methods to affect the healing process and improve the outcome of tendon repair in the future. METHODS: In a rabbit model of flexor tendon injury, tissues were harvested 3, 6, 12, and 24 days after surgery (n = 6 for each group). After RNA extraction, messenger RNA (mRNA) levels for relevant genes in tendon and tendon sheaths were measured using the reverse transcription polymerase chain reaction. Messenger RNA levels for a subset of relevant molecules at different time points after injury were compared with those of uninjured controls for tendons and tendon sheaths. RESULTS: Initially after injury, there was a shift in collagen expression with a marked increase in type III mRNA levels in both the tendon and tendon sheath, whereas those for collagen I increased only in the sheath at later time points. Aggrecan and versican mRNA levels were increased in both tissues, but temporal aspects of the changes were different. The mRNA levels for biglycan and lumican were all upregulated throughout the healing interval examined, whereas those for decorin were significantly decreased throughout in the tendon more so than the sheath. The mRNA levels for basic fibroblastic growth factor and transforming growth factor beta were elevated after injury in the tendon but not in the sheath. In contrast, mRNA levels for connective tissue growth factor were unaltered or decreased in both tissues throughout the interval assessed. CONCLUSIONS: Healing after injury to the rabbit flexor tendon and tendon sheath follow a reproducible pattern of gene expression; however, the pattern in the tendon is very different from that in the sheath. These findings indicate that interventions developed to improve healing of these tissues will have to address these differences, because they will likely affect the outcomes.

Place, publisher, year, edition, pages
2006. Vol. 31A, no 8, 1279-1287 p.
Keyword [en]
bFGF, collagen, flexor tendon, proteoglycan, TGF-B1
National Category
Surgery
Research subject
Orthopaedics
Identifiers
URN: urn:nbn:se:uu:diva-119911DOI: 10.1016/j.jhsa.2006.06.011ISI: 000241647900004PubMedID: 17027787OAI: oai:DiVA.org:uu-119911DiVA: diva2:301318
Available from: 2010-03-03 Created: 2010-03-03 Last updated: 2011-05-18Bibliographically 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)
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Biomolecular aspects of flexor tendon healing
Available from: 2010-04-15 Created: 2010-03-11 Last updated: 2010-04-16

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