| 1. |
- Forslund, Carina, et al.
(författare)
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A comparative dose-response study of cartilage-derived morphogenetic protein (CDMP)-1, -2 and -3 for tendon healing in rats
- 2003
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Ingår i: Journal of Orthopaedic Research. - 0736-0266 .- 1554-527X. ; 21:4, s. 617-621
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Tidskriftsartikel (refereegranskat)abstract
- Cartilage-derived morphogenetic proteins (CDMPs), belonging to the bone morphogenetic protein (BMP) family, are known to b cartilage and bone inducers as well as to induce tendon and ligament-like tissue. In this study we investigated the influence of CDMP-1, -2 or -3 at four different doses (0, 0.4, 2 and 10 ?g) on tendon healing in a rat model, as well as differences in osteogenesis between the different CDMPs and doses. In 110 rats, a 3 mm segment of the Achilles tendon was removed via a 2 mm skin incision. CDMP-1, -2 or -3 was injected into the defect 6 h postoperative. The rats were killed 8 days after operation. The tendon regenerates were tested biomechanically. There was a significant dose-related increase in strength and stiffness with all three CDMPs, but no difference between the CDMPs was found. Another 50 rats were used to compare the highest dose of the CDMPs with controls and osteogenic protein 1 (OP-1), as regards cartilage or bone formation after 4 weeks. Cartilage occurred in all groups, including the controls. Some specimens in all groups contained bone, except the controls. No difference between the CDMPs could be demonstrated. The CDMP-1, CDMP-3 and OP-1 groups contained significantly more calcium than controls. Only the CDMP-2 group and the controls contained significantly less calcium than the OP-1 group. In conclusion, the three CDMPs appeared similar as regards improvement of tendon repair and osteogenicity in this setting. ⌐ 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
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| 2. |
- Forslund, Carina, et al.
(författare)
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CDMP-2 induces bone or tendon-like tissue depending on mechanical stimulation
- 2002
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Ingår i: Journal of Orthopaedic Research. - 0736-0266 .- 1554-527X. ; 20:6, s. 1170-1174
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Tidskriftsartikel (refereegranskat)abstract
- Cartilage derived morphogenetic proteins (CDMPs, also known as growth and differentiation factors, GDFs) are a subgroup of the bone morphogenetic protein (BMP) gene family. As most BMPs, they are known to induce cartilage or bone formation when implanted subcutaneously or intramuscularly on an appropriate carrier. However, similar implantation experiments with CDMPs have also reported the formation of a tendon-like tissue, without any cartilage or bone. A solution to this apparent contradiction might be offered by the mechanical tissue differentiation theory, suggesting that tissue differentiation depends on the mechanical environment. This study analyzes the response to CDMP-2 implants at different sites and under different loading conditions in the rat. Collagen sponges carrying CDMP-2 were implanted subcutaneously, intramuscularly or inside a freshly created defect in the achilles tendon. Large amounts of bone were induced subcutaneously, smaller amounts intramuscularly, and in the tendons, only small amounts of bone or cartilage were seen in few animals. Thus, the amount of bone appeared inversely related to the degree of mechanical stimulus. To confirm this, CDMP was also injected into tendon defects that were either loaded or partially unloaded. All the unloaded tendons showed bone induction after one CDMP-2 injection, whereas only 4 of 10 loaded ones showed any cartilage or bone (p = 0.0005). Single injections of a similar dose of CDMP-2 have previously been shown to augment tendon repair by increasing the size of the tendon callus. This study suggests that the response to CDMP-2 is dependent on the mechanical situation at the site where it is applied. ⌐ 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
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| 3. |
- Skoglund, Björn, 1975-, et al.
(författare)
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PMMA particles and pressure - A study of the osteolytic properties of two agents proposed to cause prosthetic loosening
- 2003
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Ingår i: Journal of Orthopaedic Research. - 0736-0266 .- 1554-527X. ; 21:2, s. 196-201
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Tidskriftsartikel (refereegranskat)abstract
- Amongst the wear debris particles implicated in the particle hypothesis for prosthetic loosening are polymethylmethacrylate (PMMA), and particularly PMMA with barium sulphate contrast agent. Another suggested cause for loosening is hydrostatic pressure. PMMA particles were combined with hydrostatic pressure in a study to investigate whether there could be a synergistic or additive effect between these two factors. Titanium plates were fastened onto tibiae of 59 rats. After osseointegration, PMMA particles with barium sulphate were administered to the bone-implant interface. Further, PMMA particles were introduced into a previously published model for hydrostatic pressure induced osteolysis. There was measurable resorption in response to the PMMA particles but no additive or synergistic effect from introducing particles to the pressure model, and the effect of pressure was far greater than that of particles. These results suggest that, whereas particles can be shown to elicit an osteolytic response, the much less studied osteolytic effects of pressure could be far more important. ⌐ 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Alfredson, Håkan, et al.
(författare)
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cDNA-arrays and real-time quantitative PCR techniques in the investigation of chronic Achilles tendinosis.
- 2003
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Ingår i: Journal of Orthopaedic Research. - 0736-0266 .- 1554-527X. ; 21:6, s. 970-975
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Tidskriftsartikel (refereegranskat)abstract
- The aetiology and pathogenesis of chronic painful Achilles tendinosis are unknown. This investigation aimed to use cDNA arrays and real-time quantitative polymerase chain reaction (real-time PCR) technique to study tendinosis and control tissue samples. Five patients (females mean age 57.1+/-4.3 (years+/-SD)) with chronic painful Achilles tendinosis were included. From all patients, one biopsy was taken from the area with tendinosis and one from a clinically normal area (control) of the tendon. The tissue samples were immediately immersed in RNAlater and frozen at -80 degrees C until RNA extraction. Portions of pooled RNA from control and tendinosis sites, respectively, were transcribed to cDNA, radioactively labelled (32P), hybridized to cDNA expression arrays, and exposed to phosphoimager screens over night. Expressions of specific genes, shown to be regulated in the cDNA array analysis, were analyzed in the individual samples using real-time PCR. cDNA arrays showed that gene expressions for matrix-metalloproteinase-2 (MMP-2), fibronectin subunit B (FNRB), vascular endothelial growth factor (VEGF), and mitogen-activated protein kinase p38 (MAPKp38) were up-regulated, while matrix-metalloproteinase-3 (MMP-3) and decorin were down-regulated, in tendinosis tissue compared with control tissue. Using real-time PCR, 4/5 and 3/5 patients showed up-regulation of MMP-2 and FNRB mRNA, respectively. For decorin, VEGF, and MAPKp38, real-time PCR revealed a great variability among patients. Interestingly, the mRNAs for several cytokines and cytokine receptors were not regulated, indicating the absence of an inflammatory process in chronic painful Achilles tendinosis. In conclusion, cDNA-arrays and real-time PCR can be used to study differences in gene expression levels between tendinosis and control tendon tissue.
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| 8. |
- Alfredson, Håkan, et al.
(författare)
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High intratendinous lactate levels in painful chronic Achilles tendinosis. An investigation using microdialysis technique.
- 2002
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Ingår i: Journal of Orthopaedic Research. - 0736-0266 .- 1554-527X. ; 20:5, s. 934-938
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Tidskriftsartikel (refereegranskat)abstract
- In this investigation the microdialysis technique was used to study the concentrations of lactate in Achilles tendons with painful chronic tendinosis and in normal pain-free tendons. In four patients (mean age 40.7 years) with a painful thickening localized at the 2-6 cm level in the Achilles tendon (chronic Achilles tendinosis) and in five controls (mean age 37.2 years) with normal Achilles tendons the local concentrations of lactate were registered under resting conditions. All tendons were examined using ultrasonography. In the tendons with tendinosis the painful thickening corresponded to a widened tendon and structural tendinosis changes. Normal tendons showed no widening and a normal structure. A standard microdialysis catheter was inserted into the Achilles tendon under local anesthesia. Samplings were done every 15 min during a 4 h period. The results showed significantly higher mean concentrations of lactate in tendons with tendinosis compared to normal tendons (2.15 mmol/l vs. 1.14 mmol/l). The lactate concentrations in the tendons with tendinosis were stable, and approximately twofold higher than in the normal tendons during the whole 4 h investigation period. In conclusion, the higher concentrations of lactate in Achilles tendons with painful tendinosis indicate that there are anaerobic conditions in the area with tendinosis. The importance of this finding for the pathogenesis and pain mechanisms in this chronic condition needs to be further investigated.
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| 9. |
- Alfredson, Håkan, et al.
(författare)
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In vivo microdialysis and immunohistochemical analyses of tendon tissue demonstrated high amounts of free glutamate and glutamate NMDAR1 receptors, but no signs of inflammation, in Jumper's knee.
- 2001
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Ingår i: Journal of Orthopaedic Research. - 0736-0266 .- 1554-527X. ; 19:5, s. 881-886
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Tidskriftsartikel (refereegranskat)abstract
- This investigation describes, to our knowledge, the first experiment where the microdialysis technique was used to study certain metabolic events in human patellar tendons in combination with immunohistochemical analyses of tendon biopsies. In five patients (four men and one woman) with a long duration (range 12-36 months) of pain symptoms from Jumper's knee (localized tenderness in the patellar tendon verified as tendon changes with ultrasonography or MRI), and in five controls (four men and one woman) with normal patellar tendons, a standard microdialysis catheter was inserted into the patellar tendon under local anestesia. The local concentrations of glutamate (excitatory neurotransmitter) and prostaglandin E2 (PGE2) were registered under resting conditions. Samplings were done every 15 min during a 2 h period. In all individuals (patients and controls) biopsies were taken for immunohistochemical analyses. The results showed that it was possible to detect and measure the concentrations of glutamate and PGE2 in the patellar tendon with the use of microdialysis technique. There were significantly higher concentrations of free glutamate, but not PGE2, in tendons with tendinosis compared to normal tendons. In the biopsies, there were no inflammatory cell infiltrates, but, for the first time, it was shown that there was immunoreaction for the glutamate receptor NMDAR1 in association with nerve structures in human patellar tendons. These findings altogether indicate that glutamate might be involved in painful Jumper's knee, and further emphasizes that there is no chemical inflammation (normal PGE2 levels) in this chronic condition.
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| 10. |
- Asp, Julia, 1973, et al.
(författare)
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Alterations in the regulatory pathway involving p16, pRb and cdk4 in human chondrosarcoma.
- 2001
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Ingår i: Journal of orthopaedic research : official publication of the Orthopaedic Research Society. - 0736-0266. ; 19:1, s. 149-54
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Tidskriftsartikel (refereegranskat)abstract
- The G1 regulatory pathway involving p16, pRb and cdk4 in the cell cycle has been investigated in human chondrosarcoma. The protein expression of p16, pRb and cdk4 was analyzed by Western blot in cultured cells from eight chondrosarcomas and in two chondrosarcoma cell lines. Both cell lines and one other sample were negative for p16. Moreover, one of the cell lines was pRb-negative and showed a high expression of cdk4 as well. In the other cell line and in three other samples pRb of expected size were detected in addition to a shorter form of the protein. To further investigate the reasons for down-regulation of the p16 protein, the p16-coding gene CDKN2 was analyzed by polymerase chain reaction (PCR), methyl-specific PCR (MSP) and sequencing in all tumor samples as well as in corresponding tumor tissues from three of the samples. The p16-negative samples were all found to have homozygous deletion of CDKN2. Another sample showed partial gene methylation and a heterozygous position in codon 148 was detected in one sample. The same base substitution was also found in two of the tissue samples. Finally, cytogenetic analysis of the samples with homozygously deleted CDKN2 revealed multiple structural abnormalities in all three cases. In conclusion, the p16/pRb/cdk4 pathway may play an important role in the pathogenesis of some chondrosarcomas.
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