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Neuropeptide, mast cell and myofibroblast expression 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.
McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, Canada.
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2010 (English)In: Journal of Hand Surgery-American Volume, ISSN 0363-5023, E-ISSN 1531-6564, Vol. 35, no 11, 1842-1849 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Increased numbers of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers have been found in a number of fibrotic processes in connective tissues. The purpose of the present study was to investigate the occurrence of factors implicated in a hypothesized profibrotic neuropeptide-mast cell-myofibroblast pathway in deep flexor tendon healing.

METHODS: In a rabbit model of flexor tendon injury, with repair of the sharply transected deep flexor tendon using a modified Kessler and a running circumferential peripheral suture, segments of flexor tendons and sheaths were analyzed. The time points chosen-3, 6, 21, and 42 days after tendon repair-represent different stages in tendon healing. The messenger RNA levels of transforming growth factor-β1 and α-smooth muscle actin were measured with conventional reverse transcription-polymerase chain reaction, and the numbers of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers were determined with immunohistochemistry.

RESULTS: The messenger RNA levels for transforming growth factor-β1 and the myofibroblast marker α-smooth muscle actin were significantly increased in deep flexor tendons after injury and repair, at all studied time points, but remained unchanged or even down-regulated in the sheaths. Myofibroblasts, mast cells, and neuropeptide-containing nerve fibers all increased significantly in the healing tendons, exhibiting similar patterns of change in percentages of total cell number over time, reaching levels resembling that of the tendon sheaths with 33% to 50% of the total cell population.

CONCLUSIONS: After injury to the deep flexor tendon in a rabbit model, the proportion of myofibroblasts, mast cells, and neuropeptide-containing nerve fibers increases significantly. These findings support the hypothesis that the profibrotic neuropeptide-mast cell-myofibroblast pathway is activated in deep flexor tendon healing.

Place, publisher, year, edition, pages
2010. Vol. 35, no 11, 1842-1849 p.
Keyword [en]
a-SMA, flexor tendon healing, mast cell, myofibroblast, neuropeptide, TGF-β1
National Category
Surgery
Research subject
Orthopaedics
Identifiers
URN: urn:nbn:se:uu:diva-119917DOI: 10.1016/j.jhsa.2010.06.031ISI: 000284031400016PubMedID: 20888142OAI: oai:DiVA.org:uu-119917DiVA: diva2:301335
Available from: 2010-03-03 Created: 2010-03-03 Last updated: 2010-12-08Bibliographically 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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