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PXL01 in sodium hyaluronate results in increased PRG4 expression: a potential mechanism for anti-adhesion
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
Pergamum AB, Stockholm, Sweden.
Univ Calgary, McCaig Inst Bone & Joint Hlth, Dept Surg, Calgary, AB, Canada.
Show others and affiliations
2017 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, 28-34 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To investigate the anti-adhesive mechanisms of PXL01 in sodium hyaluronate (HA) by using the rabbit lactoferrin peptide, rabPXL01 in HA, in a rabbit model of healing tendons and tendon sheaths. The mechanism of action for PXL01 in HA is interesting since a recent clinical study of the human lactoferrin peptide PXL01 in HA administered around repaired tendons in the hand showed improved digit mobility.

MATERIALS AND METHODS: On days 1, 3, and 6 after tendon injury and surgical repair, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to assess mRNA expression levels for genes encoding the mucinous glycoprotein PRG4 (also called lubricin) and a subset of matrix proteins, cytokines, and growth factors involved in flexor tendon repair. RabPXL01 in HA was administered locally around the repaired tendons, and mRNA expression was compared with untreated repaired tendons and tendon sheaths.

RESULTS: We observed, at all time points, increased expression of PRG4 mRNA in tendons treated with rabPXL01 in HA, but not in tendon sheaths. In addition, treatment with rabPXL01 in HA led to repression of the mRNA levels for the pro-inflammatory mediators interleukin (IL)-1β, IL-6, and IL-8 in tendon sheaths.

CONCLUSIONS: RabPXL01 in HA increased lubricin mRNA production while diminishing mRNA levels of inflammatory mediators, which in turn reduced the gliding resistance and inhibited the adhesion formation after flexor tendon repair.

Place, publisher, year, edition, pages
2017. Vol. 122, no 1, 28-34 p.
Keyword [en]
Carcinoid heart disease, Cardiac imaging, Heart metastases, Neuroendocrine tumors
National Category
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-309615DOI: 10.1080/03009734.2016.1230157ISI: 000396476600004PubMedID: 27658527OAI: oai:DiVA.org:uu-309615DiVA: diva2:1052309
Funder
Swedish Foundation for Strategic Research
Available from: 2016-12-06 Created: 2016-12-06 Last updated: 2017-04-12Bibliographically approved
In thesis
1. Intrasynovial flexor tendon injuries and repair
Open this publication in new window or tab >>Intrasynovial flexor tendon injuries and repair
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Complications after surgical repair of intrasynovial flexor tendon injuries in the hand occur despite advanced suture techniques and structured postoperative rehabilitation regimens. Early controlled tendon mobilization prevents adhesion formations and improves tendon healing as well as digit range of motion. To allow early postoperative rehabilitation, the strength of the repair must withstand forces created during the rehabilitation maneuvers. Improvements in suture biomechanics have increased repair strength, but up to 18 percent of repaired tendons still rupture. The overarching aim of this thesis was to investigate how to best treat intrasynovial flexor tendon injuries with limited risk of repair rupture, decreased adhesion formations, and to estimate the effect of individual patient and injury characteristics on functional outcome.

In two observational studies, we identified risk factors for rupture of repaired intrasynovial flexor digitorum profundus (FDP) tendons, and studied effects of these risk factors on the long-term outcome. Age was associated with increased risk of repair rupture and impaired digital mobility the first year after surgical repair. Concomitant flexor digitorum superficialis (FDS) transection was associated with increased risk of repair rupture without affecting digital mobility. Concomitant nerve transection lowered the rupture risk without affecting digital mobility.

To better understand forces generated in the flexor tendons during rehabilitation maneuvers, we measured in vivo forces in the index finger FDP and FDS tendons during rehabilitation exercises. Highest forces were measured during isolated FDP and FDS flexion for the FDP and FDS respectively. For the FDS tendon, higher forces were observed with the wrist at 30° flexion compared to neutral position, and for the FDP tendon, forces were higher during active finger flexion compared to place and hold.

PXL01 is a lactoferrin peptide with anti-adhesive effects previously demonstrated in animal studies and a clinical trial to improve digital mobility when administrated around repaired tendons. We studied the mechanism of action of its corresponding rabbit peptide, rabPXL01 in sodium hyaluronate (HA) in a rabbit model of flexor tendon transection and repair and used RT-qPCR to assess mRNA levels for different genes. Increased levels of PRG4 (encoding lubricin) were observed in rabPXL01 in HA treated tendons. The expression of Interleukin 1β, 6, and 8 was repressed in tendon sheaths. RabPXL01 in HA might stimulate the release of lubricin and diminish inflammation, which correspondingly reduces tendon-gliding resistance and adhesion formations during postoperative rehabilitation exercises.

The results of this thesis suggest individually adapted treatment plans, depending on repair strength, patient and injury characteristics, as a possible way to improve outcome after flexor tendon repair.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 67 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1307
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-316559 (URN)978-91-554-9838-2 (ISBN)
Public defence
2017-04-28, Hedstrandsalen, Akademiska sjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2017-04-04 Created: 2017-03-02 Last updated: 2017-04-18

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