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Eliasson, Pernilla
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Bernhardsson, M., Dietrich, F., Tätting, L., Eliasson, P. & Aspenberg, P. (2019). Depletion of cytotoxic (CD8+) T cells impairs implant fixation in rat cancellous bone. Journal of Orthopaedic Research, 37(4), 805-811
Öppna denna publikation i ny flik eller fönster >>Depletion of cytotoxic (CD8+) T cells impairs implant fixation in rat cancellous bone
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2019 (Engelska)Ingår i: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 37, nr 4, s. 805-811Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

As cytotoxic (CD8(+)) T cells seem to impair shaft fracture healing, we hypothesized that depletion of CD8(+) cells would instead improve healing of cancellous bone. Additionally, we also tested if CD8-depletion would influence the healing of ruptured Achilles tendons. Rats received a single injection of either anti-CD8 antibodies or saline and put through surgery 24 h later. Three different surgical interventions were performed as follows: (1) a drill hole in the proximal tibia with microCT (BV/TV) to assess bone formation; (2) a screw in the proximal tibia with mechanical evaluation (pull-out force) to assess fracture healing; (3) Achilles tendon transection with mechanical evaluation (force-at-failure) to assess tendon healing. Furthermore, CD8-depletion was confirmed with flow cytometry on peripheral blood. Flow cytometric analysis confirmed depletion of CD8(+) cells (p amp;lt; 0.001). Contrary to our hypothesis, depletion of CD8(+) cells reduced the implant pull-out force by 19% (p amp;lt; 0.05) and stiffness by 34% (p amp;lt; 0.01), although the bone formation in the drill holes was the same as in the controls. Tendon healing was unaffected by CD8-depletion. Our results suggest that CD8(+) cells have an important part in cancellous bone healing.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2019
Nyckelord
bone healing; cancellous; tendon healing; cytotoxic T cells; CD8 depletion
Nationell ämneskategori
Ortopedi
Identifikatorer
urn:nbn:se:liu:diva-157559 (URN)10.1002/jor.24246 (DOI)000467082100001 ()30737834 (PubMedID)2-s2.0-85062344231 (Scopus ID)
Anmärkning

Funding Agencies|Swedish Research Council [2031-47-5]; AFA insurance company EU 159 7th framework program [FP7/2007-2013, 279239]; Linkoping 160 University

Tillgänglig från: 2019-06-22 Skapad: 2019-06-22 Senast uppdaterad: 2019-06-25Bibliografiskt granskad
Alim, A., Ackermann, P. W., Eliasson, P., Blomgran, P., Kristiansson, P., Pejler, G. & Peterson, M. (2017). Increased mast cell degranulation and co-localization of mast cells with the NMDA receptor-1 during healing after Achilles tendon rupture. Cell and Tissue Research, 370(3), 451-460
Öppna denna publikation i ny flik eller fönster >>Increased mast cell degranulation and co-localization of mast cells with the NMDA receptor-1 during healing after Achilles tendon rupture
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2017 (Engelska)Ingår i: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 370, nr 3, s. 451-460Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The role of inflammation and the mechanism of tendon healing after rupture has historically been a matter of controversy. The purpose of the present study is to investigate the role of mast cells and their relation to the NMDA receptor-1 (a glutamate receptor) during healing after Achilles tendon rupture. Eight female Sprague Dawley rats had their right Achilles tendon transected. Three weeks after rupture, histological quantification of mast cell numbers and their state of degranulation was assessed by histochemistry. Co-localization of mast cell tryptase (a mast cell marker) and NMDA receptor-1 was determined by immunofluorescence. The intact left Achilles tendon was used as control. An increased number of mast cells and a higher proportion of degranulated mast cells were found in the healing Achilles tendon compared to the intact. In addition, increased co-localization of mast cell tryptase and NMDA receptor-1 was seen in the areas of myotendinous junction, mid-tendon proper and bone tendon junction of the healing versus the intact tendon. These findings introduce a possible role for mast cells in the healing phase after Achilles tendon rupture.

Ort, förlag, år, upplaga, sidor
SPRINGER, 2017
Nyckelord
Achilles tendon healing; NMDA; Mast cells; Tryptase; Rats
Nationell ämneskategori
Cell- och molekylärbiologi
Identifikatorer
urn:nbn:se:liu:diva-143611 (URN)10.1007/s00441-017-2684-y (DOI)000416358400010 ()28975451 (PubMedID)
Anmärkning

Funding Agencies|AFA Forsakring; Swedish Research Council

Tillgänglig från: 2017-12-13 Skapad: 2017-12-13 Senast uppdaterad: 2018-04-19
Eliasson, P., Svensson, R. B., Giannopoulos, A., Eismark, C., Kjaer, M., Schjerling, P. & Heinemeier, K. M. (2017). Simvastatin and atorvastatin reduce the mechanical properties of tendon constructs in vitro and introduce catabolic changes in the gene expression pattern. PLoS ONE, 12(3), Article ID e0172797.
Öppna denna publikation i ny flik eller fönster >>Simvastatin and atorvastatin reduce the mechanical properties of tendon constructs in vitro and introduce catabolic changes in the gene expression pattern
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2017 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 3, artikel-id e0172797Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Treatment with lipid-lowering drugs, statins, is common all over the world. Lately, the occurrence of spontaneous tendon ruptures or tendinosis have suggested a negative influence of statins upon tendon tissue. But how statins might influence tendons is not clear. In the present study, we investigated the effect of statin treatment on mechanical strength, cell proliferation, collagen content and gene expression pattern in a tendon-like tissue made from human tenocytes in vitro. Human tendon fibroblasts were grown in a 3D tissue culture model (tendon constructs), and treated with either simvastatin or atorvastatin, low or high dose, respectively, for up to seven days. After seven days of treatment, mechanical testing of the constructs was performed. Collagen content and cell proliferation were also determined. mRNA levels of several target genes were measured after one or seven days. The maximum force and stiffness were reduced by both statins after 7 days (pamp;lt;0.05), while the cross sectional area was unaffected. Further, the collagen content was reduced by atorvastatin (p = 0.01) and the cell proliferation rate was decreased by both types of statins (pamp;lt;0.05). Statin treatment also introduced increased mRNA levels of MMP-1, MMP-3, MMP-13, TIMP-1 and decreased levels of collagen type 1 and 3. In conclusion, statin treatment appears to have a negative effect on tendon matrix quality as seen by a reduced strength of the tendon constructs. Further, activated catabolic changes in the gene expression pattern and a reduced collagen content indicated a disturbed balance in matrix production of tendon due to statin administration.

Ort, förlag, år, upplaga, sidor
PUBLIC LIBRARY SCIENCE, 2017
Nationell ämneskategori
Farmakologi och toxikologi
Identifikatorer
urn:nbn:se:liu:diva-136042 (URN)10.1371/journal.pone.0172797 (DOI)000396054300018 ()28264197 (PubMedID)
Anmärkning

Funding Agencies|Lundbeck Foundation; Nordea Foundation; IOC Sports medicine Copenhagen; Danish Medical Research Council [0602-02960B]; Swedish Society for Medical Research; Magnus Bergyall Foundation; Lions research foundation

Tillgänglig från: 2017-03-27 Skapad: 2017-03-27 Senast uppdaterad: 2018-05-02
Khayyeri, H., Gustafsson, A., Heuijerjans, A., Matikainen, M. K., Julkunen, P., Eliasson, P., . . . Isaksson, H. (2015). A Fibre-Reinforced Poroviscoelastic Model Accurately Describes the Biomechanical Behaviour of the Rat Achilles Tendon. PLoS ONE, 10(6), Article ID e0126869.
Öppna denna publikation i ny flik eller fönster >>A Fibre-Reinforced Poroviscoelastic Model Accurately Describes the Biomechanical Behaviour of the Rat Achilles Tendon
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2015 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 6, artikel-id e0126869Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background Computational models of Achilles tendons can help understanding how healthy tendons are affected by repetitive loading and how the different tissue constituents contribute to the tendons biomechanical response. However, available models of Achilles tendon are limited in their description of the hierarchical multi-structural composition of the tissue. This study hypothesised that a poroviscoelastic fibre-reinforced model, previously successful in capturing cartilage biomechanical behaviour, can depict the biomechanical behaviour of the rat Achilles tendon found experimentally. Materials and Methods We developed a new material model of the Achilles tendon, which considers the tendons main constituents namely: water, proteoglycan matrix and collagen fibres. A hyperelastic formulation of the proteoglycan matrix enabled computations of large deformations of the tendon, and collagen fibres were modelled as viscoelastic. Specimen-specific finite element models were created of 9 rat Achilles tendons from an animal experiment and simulations were carried out following a repetitive tensile loading protocol. The material model parameters were calibrated against data from the rats by minimising the root mean squared error (RMS) between experimental force data and model output. Results and Conclusions All specimen models were successfully fitted to experimental data with high accuracy (RMS 0.42-1.02). Additional simulations predicted more compliant and soft tendon behaviour at reduced strain-rates compared to higher strain-rates that produce a stiff and brittle tendon response. Stress-relaxation simulations exhibited strain-dependent stress-relaxation behaviour where larger strains produced slower relaxation rates compared to smaller strain levels. Our simulations showed that the collagen fibres in the Achilles tendon are the main load-bearing component during tensile loading, where the orientation of the collagen fibres plays an important role for the tendons viscoelastic response. In conclusion, this model can capture the repetitive loading and unloading behaviour of intact and healthy Achilles tendons, which is a critical first step towards understanding tendon homeostasis and function as this biomechanical response changes in diseased tendons.

Ort, förlag, år, upplaga, sidor
Public Library of Science, 2015
Nationell ämneskategori
Ortopedi Teknisk mekanik
Identifikatorer
urn:nbn:se:liu:diva-120290 (URN)10.1371/journal.pone.0126869 (DOI)000356630900035 ()26030436 (PubMedID)
Anmärkning

Funding Agencies|Marie Curie Intra-European Fellowship for Career Development [PIEF-GA-2012-626941]; Academy of Finland [259543]

Tillgänglig från: 2015-07-24 Skapad: 2015-07-24 Senast uppdaterad: 2018-01-11
Sandberg, O., Dånmark, I., Eliasson, P. & Aspenberg, P. (2015). Influence of a lower leg brace on traction force in healthy and ruptured Achilles tendons. MLTJ Muscles, Ligaments and Tendons Journal, 5(2), 63-67
Öppna denna publikation i ny flik eller fönster >>Influence of a lower leg brace on traction force in healthy and ruptured Achilles tendons
2015 (Engelska)Ingår i: MLTJ Muscles, Ligaments and Tendons Journal, ISSN 2240-4554, Vol. 5, nr 2, s. 63-67Artikel i tidskrift (Övrigt vetenskapligt) Published
Abstract [en]

Background: we investigated how ruptured Achilles tendons are loaded in a brace. There is an ongoing discussion whether patients should be recommended to bear weight on the injuredlimb. However, little is known about the effects of bracing on tensional loading of the healing Achilles tendon: it is uncertain if load-bearing actually stresses the Achilles tendon inside a brace.

Methods: we measured plantar flexion moment inside the brace, in order to estimate tensional loading of the tendon, by use of an insole with pressure transducers.

Results: after wearing the brace for 1 hour, young healthy individuals reduced their maximum flexion moment during gait by half. Patients with Achilles tendon rupture showed no measurable flexion moment during gait with the brace, 4 or 7 weeks after injury. Only when specifically instructed, they could produce a considerable plantar flexion moment. We noted that gait speed with the brace at 4 weeks correlated with a heel-raise functional test at 1 year: the higher the spontaneous gait speed, the less the functional difference between the injured and the uninjured leg (r2=0.68; p=0.002).

Conclusion: the correlation with gait speed suggests that the patients’ general physical aptness has an impact on the end result.

Ort, förlag, år, upplaga, sidor
Rome, Italy: C I C Edizioni Internazionali, 2015
Nyckelord
Achilles tendon rupture; bracing; immobilization; loading; flexion moment
Nationell ämneskategori
Ortopedi
Identifikatorer
urn:nbn:se:liu:diva-125335 (URN)10.11138/mltj/2015.5.2.063 (DOI)26261783 (PubMedID)
Tillgänglig från: 2016-02-19 Skapad: 2016-02-19 Senast uppdaterad: 2018-01-10Bibliografiskt granskad
Hammerman, M., Aspenberg, P. & Eliasson, P. (2014). Microtrauma stimulates rat Achilles tendon healing via an early gene expression pattern similar to mechanical loading. Journal of applied physiology, 116(1), 54-60
Öppna denna publikation i ny flik eller fönster >>Microtrauma stimulates rat Achilles tendon healing via an early gene expression pattern similar to mechanical loading
2014 (Engelska)Ingår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 116, nr 1, s. 54-60Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Mechanical loading increases the strength of healing tendons, but also induces small localized bleedings. Therefore, it is unclear if increased strength after loading is a response to mechanotransduction or microtrauma. We have previously found only five genes to be up-regulated 15 min after a single loading episode, of them four were transcription factors. These genes are followed by hundreds of genes after 3 h, many of them involved in inflammation. We now compared healing in mechanically unloaded tendons with or without added microtrauma induced by needling of the healing tissue. Nineteen rats received Botox into the calf muscle to reduce loading, and the Achilles tendon was transected. Ten rats were randomized to needling days 2-5. Mechanical testing on day 8 showed increased strength by 45% in the needling group. Next, another 24 rats were similarly unloaded, and 16 randomized to needling on day 5 after transection. Nineteen characteristic genes, known to be regulated by loading in this model, were analyzed by qRT-PCR. Four of these genes were regulated 15 min after needling. Three of them (Egr1, c-Fos, Rgs1) were among the five regulated genes after loading in a previous study. Sixteen of the 19 genes were regulated after 3 h, in the same way as after loading. In conclusion, needling increased strength, and there was a striking similarity between the gene expression response to needling and mechanical loading. This suggests that the response to loading in early tendon healing can, at least in part, be a response to microtrauma.

Ort, förlag, år, upplaga, sidor
American Physiological Society, 2014
Nyckelord
qRT-PCR; unloading; mechanical testing; early response genes; inflammation
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-103870 (URN)10.1152/japplphysiol.00741.2013 (DOI)000329196100008 ()
Tillgänglig från: 2014-01-31 Skapad: 2014-01-30 Senast uppdaterad: 2018-02-20
Lundin, A.-C., Aspenberg, P. & Eliasson, P. T. (2014). Trigger finger, tendinosis, and intratendinous gene expression. Scandinavian Journal of Medicine and Science in Sports, 24(2), 363-368
Öppna denna publikation i ny flik eller fönster >>Trigger finger, tendinosis, and intratendinous gene expression
2014 (Engelska)Ingår i: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 24, nr 2, s. 363-368Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The pathogenesis of trigger finger has generally been ascribed to primary changes in the first annular ligament. In contrast, we recently found histological changes in the tendons, similar to the findings in Achilles tendinosis or tendinopathy. We therefore hypothesized that trigger finger tendons would show differences in gene expression in comparison to normal tendons in a pattern similar to what is published for Achilles tendinosis. We performed quantitative real-time polymerase chain reaction on biopsies from finger flexor tendons, 13 trigger fingers and 13 apparently healthy control tendons, to assess the expression of 10 genes which have been described to be differently expressed in tendinosis (collagen type 1a1, collagen 3a1, MMP-2, MMP-3, ADAMTS-5, TIMP-3, aggrecan, biglycan, decorin, and versican). In trigger finger tendons, collagen types 1a1 and 3a1, aggrecan and biglycan were all up-regulated, and MMP-3and TIMP-3 were down-regulated. These changes were statistically significant and have been previously described for Achilles tendinosis. The remaining four genes were not significantly altered. The changes in gene expression support the hypothesis that trigger finger is a form of tendinosis. Because trigger finger is a common condition, often treated surgically, it could provide opportunities for clinical research on tendinosis.

Ort, förlag, år, upplaga, sidor
Wiley, 2014
Nyckelord
tendinopathy; tendinosis; stenosing tendovaginitis; tendovaginitis stenosans; quantitative real-time PCR; qPCR
Nationell ämneskategori
Ortopedi Cell- och molekylärbiologi
Identifikatorer
urn:nbn:se:liu:diva-106131 (URN)10.1111/j.1600-0838.2012.01514.x (DOI)000332982700018 ()
Tillgänglig från: 2014-04-25 Skapad: 2014-04-24 Senast uppdaterad: 2018-01-11
Eliasson, P., Andersson, T., Hammerman, M. & Aspenberg, P. (2013). Primary gene response to mechanical loading in healing rat Achilles tendons. Journal of applied physiology, 114(11), 1519-1526
Öppna denna publikation i ny flik eller fönster >>Primary gene response to mechanical loading in healing rat Achilles tendons
2013 (Engelska)Ingår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 114, nr 11, s. 1519-1526Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Loading can stimulate tendon healing. In healing rat Achilles tendons, we have found more than 150 genes upregulated or downregulated 3 h after one loading episode. We hypothesized that these changes were preceded by a smaller number of regulatory genes and thus performed a microarray 15 min after a short loading episode, to capture the primary response to loading. We transected the Achilles tendon of 54 rats and allowed them to heal. The hind limbs were unloaded by tail-suspension during the entire experiment, except during the loading episode. The healing tendon tissue was analyzed by mechanical testing, microarray, and quantitative real-time polymerase chain reaction (qRT-PCR). Mechanical testing showed that 5 min of loading each day for 4 days created stronger tissue. The microarray analysis after one loading episode identified 15 regulated genes. Ten genes were analyzed in a repeat experiment with new rats using qRT-PCR. This confirmed the increased expression of four genes: early growth response 2 (Egr2), c-Fos, FosB, and regulation of G protein signaling 1 (Rgs1). The other genes were unaltered. We also analyzed the expression of early growth response 1 (Egr1), which is often coregulated with c-Fos or Egr2, and found that this was also increased after loading. Egr1, Egr2, c-Fos, and FosB are transcription factors that can be triggered by numerous stimuli. However, Egr1 and Egr2 are necessary for normal tendon development, and can induce ectopic expression of tendon markers. The five regulated genes appear to constitute a general activation machinery. The further development of gene regulation might depend on the tissue context.

Ort, förlag, år, upplaga, sidor
American Physiological Society, 2013
Nyckelord
tail-suspension; treadmill walking; tendon repair; early growth response; microarray
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-96124 (URN)10.1152/japplphysiol.01500.2012 (DOI)000319804600005 ()
Tillgänglig från: 2013-08-14 Skapad: 2013-08-14 Senast uppdaterad: 2017-12-06
Andersson, T., Eliasson, P. & Aspenberg, P. (2012). Achilles tendon healing in rats is improved by intermittent mechanical loading during the inflammatory phase. Journal of Orthopaedic Research, 30(2), 274-279
Öppna denna publikation i ny flik eller fönster >>Achilles tendon healing in rats is improved by intermittent mechanical loading during the inflammatory phase
2012 (Engelska)Ingår i: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 30, nr 2, s. 274-279Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Tendons adapt to changes in mechanical loading, and numerous animal studiesshow that immobilization of a healing tendon is detrimental to the healingprocess. The present study addresses whether the effects of a few episodes ofmechanical loading are different during different phases of healing. Fifty femalerats underwent Achilles tendon transection, and their hind limbs were unloadedby tail suspension on the day after surgery. One group of 10 rats was taken downfrom suspension to walk on a treadmill for 30 minutes per day, on days 2-5 aftertransection. They were euthanized on day 8. Another group underwent similartreadmill running on days 8-11 and was euthanized on day 14. Completelyunloaded groups were euthanized on day 8 and 14. Tendon specimens were thenevaluated mechanically. The results showed that just 4 loading episodesincreased the strength of the healing tendon. This was evident irrespective of thetime-point when loading was applied (early or late). The positive effect on earlyhealing was unexpected, considering that the mechanical stimulation was appliedduring the inflammatory phase, when the calluses were small and fragile. Ahistological study of additional groups with early loading also showed someincreased bleeding in the loaded calluses. Our results indicate that a smallamount of early loading may improve the outcome of tendon healing. This couldbe of interest to clinical practice.

Ort, förlag, år, upplaga, sidor
Wiley Online Library, 2012
Nyckelord
Early loading, tail-suspension, unloading, mechanical testing, cell differentiation
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-70772 (URN)10.1002/jor.21511 (DOI)000298581200016 ()
Anmärkning

funding agencies|Swedish National Centre for Research in Sports||Swedish Research Council| VR 2009-6725 |Ostergotland County Council||

Tillgänglig från: 2011-09-16 Skapad: 2011-09-16 Senast uppdaterad: 2017-12-08Bibliografiskt granskad
Björnsson Hallgren, H. C., Eliasson, P. T., Aspenberg, P. & Adolfsson, L. (2012). Elevated plasma levels of TIMP-1 in patients with rotator cuff tear. Acta Orthopaedica, 83(5), 523-528
Öppna denna publikation i ny flik eller fönster >>Elevated plasma levels of TIMP-1 in patients with rotator cuff tear
2012 (Engelska)Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 83, nr 5, s. 523-528Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background and purpose:Extracellular matrix remodelling is altered in rotator cuff tears,16partly due to altered expression of matrix metalloproteinases (MMPs) and their inhibitors. It is unclear if this altered expression can be traced as changes in plasma protein levels.

The purposes were to measure the plasma level of MMPs and their tissue inhibitors (TIMPs) inpatients with rotator cuff tears and to relate changes in the pattern of MMP and TIMP levels with the extent of the rotator cuff tear.

Methods: Blood samples were collected from 17 patients, median 61 (range 39-77) years, with sonographically verified rotator cuff tears (partial- or full-thickness). These were compared with 16 gender and age matched control persons with sonographically intact rotator cuffs. Plasma levels of MMPs and TIMPs were measured simultaneously using Luminex technology and ELISA.

Results: The plasma level of TIMP-1 was elevated in patients with rotator cuff tears, especially in those with full-thickness tears. The levels of TIMP-1, TIMP-3 and MMP-9 were higher in patients with full-thickness tears compared to those with partial-thickness tears, but only TIMP-1 was different from controls.

Interpretation: The observed elevation of TIMP-1 in plasma might reflect local pathological processes in or around the rotator cuff, or a genetic predisposition in these patients. That levels of TIMP-1 and certain MMP´s was found to differ between partial and full thickness tears may reflect the extent of the lesion or different aetiology and pathomechanisms.

Nyckelord
Rotator cuff tear, matrix metalloproteinases, ultrasound, degeneration
Nationell ämneskategori
Ortopedi
Identifikatorer
urn:nbn:se:liu:diva-82116 (URN)10.3109/17453674.2012.736174 (DOI)000310015700015 ()
Tillgänglig från: 2012-10-01 Skapad: 2012-10-01 Senast uppdaterad: 2018-01-12Bibliografiskt granskad
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