| 1. |
- Berglund, Maria, 1975-, et al.
(författare)
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Assessment of mRNA levels for matrix molecules and TGF-B1 in rabbit flexor and peroneus tendons reveals regional differences in steady-state expression
- 2004
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Ingår i: Journal of Hand Surgery - British and European Volume. - : SAGE Publications. - 0266-7681 .- 1532-2211. ; 29:2, s. 165-169
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Tidskriftsartikel (refereegranskat)abstract
- This study analysed the differences on a molecular level between two segments of the deep flexor tendon, and compared the intrasynovial flexor tendon with the tendon sheath and the extrasynovial peroneus tendon in a rabbit model. The TRIspin method of RNA extraction was combined with the reverse transcription polymerase chain reaction to assess mRNA levels in the tissue segments. Significant differences were detected for all genes studied. mRNA levels for aggrecan, biglycan and collagen III were significantly higher in the fibrocartilaginous proximal segment of the flexor tendon. Collagen I was higher in the flexor tendon than the sheath and the peroneus tendon, and TGF-beta1 was significantly lower in the peroneus tendon. This study demonstrates differences at the mRNA level between different segments of tendon, indicating that the tendon tissue may be adapted to its environment.
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| 2. |
- Berglund, Maria, 1975-, et al.
(författare)
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Growth Factor and Protease Expression during Different Phases of Healing after Rabbit Deep Flexor Tendon Repair
- 2011
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Ingår i: Journal of Orthopaedic Research. - : Wiley. - 0736-0266 .- 1554-527X. ; 29:6, s. 886-892
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Berglund, Maria, 1975-, et al.
(författare)
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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
- 2006
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Ingår i: Journal of Hand Surgery-American Volume. - : Elsevier BV. - 0363-5023 .- 1531-6564. ; 31A:8, s. 1279-1287
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Edsfeldt, Sara, et al.
(författare)
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PXL01 in sodium hyaluronate results in increased PRG4 expression : a potential mechanism for anti-adhesion
- 2017
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 122:1, s. 28-34
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Huisman, Elise S., et al.
(författare)
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Regional molecular and cellular differences in the female rabbit Achilles tendon complex : potential implications for understanding responses to loading
- 2014
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Ingår i: Journal of Anatomy. - : Wiley. - 0021-8782 .- 1469-7580. ; 224:5, s. 538-547
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was: (i) to analyze the morphology and expression of extracellular matrix genes in six different regions of the Achilles tendon complex of intact normal rabbits; and (ii) to assess the effect of ovariohysterectomy (OVH) on the regional expression of these genes. Female New Zealand White rabbits were separated into two groups: (i) intact normal rabbits (n = 4); and (ii) OVH rabbits (n = 8). For each rabbit, the Achilles tendon complex was dissected into six regions: distal gastrocnemius (DG); distal flexor digitorum superficialis; proximal lateral gastrocnemius (PLG); proximal medial gastrocnemius; proximal flexor digitorum superficialis; and paratenon. For each of the regions, hematoxylin and eosin staining was performed for histological evaluation of intact normal rabbit tissues and mRNA levels for proteoglycans, collagens and genes associated with collagen regulation were assessed by real-time reverse transcription-quantitative polymerase chain reaction for both the intact normal and OVH rabbit tissues. The distal regions displayed a more fibrocartilaginous phenotype. For intact normal rabbits, aggrecan mRNA expression was higher in the distal regions of the Achilles tendon complex compared with the proximal regions. Collagen Type I and matrix metalloproteinase-2 expression levels were increased in the PLG compared to the DG in the intact normal rabbit tissues. The tendons from OVH rabbits had lower gene expressions for the proteoglycans aggrecan, biglycan, decorin and versican compared with the intact normal rabbits, although the regional differences of increased aggrecan expression in distal regions compared with proximal regions persisted. The tensile and compressive forces experienced in the examined regions may be related to the regional differences found in gene expression. The lower mRNA expression of the genes examined in the OVH group confirms a potential effect of systemic estrogen on tendon.
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