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Andersson, Therese
Publications (10 of 13) Show all publications
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
Open this publication in new window or tab >>Primary gene response to mechanical loading in healing rat Achilles tendons
2013 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 114, no 11, p. 1519-1526Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
American Physiological Society, 2013
Keywords
tail-suspension; treadmill walking; tendon repair; early growth response; microarray
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-96124 (URN)10.1152/japplphysiol.01500.2012 (DOI)000319804600005 ()
Available from: 2013-08-14 Created: 2013-08-14 Last updated: 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
Open this publication in new window or tab >>Achilles tendon healing in rats is improved by intermittent mechanical loading during the inflammatory phase
2012 (English)In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 30, no 2, p. 274-279Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
Wiley Online Library, 2012
Keywords
Early loading, tail-suspension, unloading, mechanical testing, cell differentiation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-70772 (URN)10.1002/jor.21511 (DOI)000298581200016 ()
Note

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

Available from: 2011-09-16 Created: 2011-09-16 Last updated: 2017-12-08Bibliographically approved
Sandberg, O., Eliasson, P. T., Andersson, T., Agholme, F. & Aspenberg, P. (2012). Etanercept does not impair healing in rat models of tendon or metaphyseal bone injury. Acta Orthopaedica, 83(3), 305-310
Open this publication in new window or tab >>Etanercept does not impair healing in rat models of tendon or metaphyseal bone injury
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2012 (English)In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 83, no 3, p. 305-310Article in journal (Refereed) Published
Abstract [en]

Background and purpose Should blockade of TNF-alpha be avoided after orthopedic surgery? Healing of injuries in soft tissues and bone starts with a brief inflammatory phase. Modulation of inflammatory signaling might therefore interfere with healing. For example, Cox inhibitors impair healing in animal models of tendon, ligament, and bone injury, as well as in fracture patients. TNF-alpha is expressed locally at increased levels during early healing of these tissues. We therefore investigated whether blocking of TNF-alpha with etanercept influences the healing process in established rat models of injury of tendons and metaphyseal bone. less thanbrgreater than less thanbrgreater thanMethods Rats were injected with etanercept, 3.5 mg/kg 3 times a week. Healing of transected Achilles tendons and bone healing around screws implanted in the tibial metaphysis were estimated by mechanical testing. Tendons were allowed to heal either with or without mechanical loading. Ectopic bone induction following intramuscular BMP-2 implants has previously been shown to be stimulated by etanercept in rodents. This was now tested as a positive control. less thanbrgreater than less thanbrgreater thanResults Tendon peak force after 10 days was not significantly influenced by etanercept. Changes exceeding 29% could be excluded with 95% confidence. Likewise, screw pull-out force was not significantly influenced. More than 25% decrease or 18% increase could be excluded with 95% confidence. However, etanercept treatment increased the amount of bone induced by intramuscular BMP-2 implants, as estimated by blind histological scoring. less thanbrgreater than less thanbrgreater thanInterpretation Etanercept does not appear to impair tendon or metaphyseal bone healing to any substantial degree.

Place, publisher, year, edition, pages
Informa Healthcare, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79101 (URN)10.3109/17453674.2012.693018 (DOI)000304781000018 ()
Note

Funding Agencies|Swedish Research Council|2009-6725|Linkoping University, Ostergotland County Council, Swedish Centre for Research in Sports||King Gustaf V and Queen Victoria Free Mason Foundation||

Available from: 2012-06-29 Created: 2012-06-29 Last updated: 2017-12-07
Andersson, T., Eliasson, P. & Aspenberg, P. (2012). Growth hormone does not stimulate early healing in rat tendons. International Journal of Sports Medicine, 33(3), 240-243
Open this publication in new window or tab >>Growth hormone does not stimulate early healing in rat tendons
2012 (English)In: International Journal of Sports Medicine, ISSN 0172-4622, E-ISSN 1439-3964, Vol. 33, no 3, p. 240-243Article in journal (Refereed) Published
Abstract [en]

Growth Hormone stimulates bone growth and fracture repair. It acts mainly by increasing the systemic levels of IGF-1. Local treatment with IGF-1 appears to stimulate tendon healing. We therefore hypothesized that systemic treatment with Growth Hormone would also stimulate tendon healing. Rat Achilles tendons were transected and left to heal. 4 groups were studied. Intramuscular injections of botulinum toxin A (Botox) were used to reduce loading in 2 groups. The animals were randomized to twice daily injections of Growth Hormone (n=2×10) or saline (n=2×10), and killed after 10 days. Healing was assessed by mechanical testing. Muscle paralysis induced by Botox reduced the strength of the healing tendon by two thirds. Growth Hormone increased femoral and tibial length in the unloaded, and femoral and tibial weight in the loaded group. Body weight and muscle weight were increased in both. In contrast, there was no increase in the strength of the healing tendons, regardless of mechanical loading status. An increase in peak force of the loaded healing tendons by more than 5% could be excluded with 95% confidence. In spite of its stimulatory effects on other tissues, Growth Hormone did not appear to stimulate tendon or tendon repair.

Place, publisher, year, edition, pages
Stuttgart: Georg Thieme Verlag KG, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-76085 (URN)10.1055/s-0031-1291324 (DOI)000301005800012 ()22318558 (PubMedID)
Note
funding agencies|Swedish Research council| 2009-6725 |Swedish National Center for Research in Sports||Available from: 2012-03-26 Created: 2012-03-26 Last updated: 2017-12-07
Eliasson, P., Andersson, T. & Aspenberg, P. (2012). Influence of a single loading episode on gene expression in healing rat Achilles tendons. Journal of applied physiology, 112(2), 279-288
Open this publication in new window or tab >>Influence of a single loading episode on gene expression in healing rat Achilles tendons
2012 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 112, no 2, p. 279-288Article in journal (Refereed) Published
Abstract [en]

Mechanical loading stimulates tendon healing via mechanisms that are largely unknown. Genes will be differently regulated in loaded healing tendons, compared to unloaded, just because of the fact that healing processes have been changed. In order to avoid such secondary effects and study the effect of loading per se, we therefore studied the gene expression response shortly after a single loading episode in otherwise unloaded healing tendons.

The Achilles tendon was transected in 30 tail suspended rats. The animals were let down from the suspension to load their tendons on a treadmill for 30 min once, 5 days after tendon transection. Gene expression was studied by Affymetrix microarray before, and 3, 12, 24 and 48 h after loading. The strongest response in gene expression was seen 3 hours after loading, when 150 genes were up- or down-regulated (fold change≥ 2, p≤0.05). 12 hours after loading, only 3 genes were up-regulated, while 38 were down-regulated. Less than 7 genes were regulated after 24 and 48 hours. Genes involved in the inflammatory response were strongly regulated at 3 and 12 hours after loading; this included up-regulation of iNOS, PGE synthase, and IL-1β. Also genes involved in wound healing/coagulation, angiogenesis and production of reactive oxygen species were strongly regulated by loading. Microarray results were confirmed for 14 selected genes in a repeat experiment (N=30 rats) using real-time PCR. It was also confirmed that a single loading episode on day 5 increased the strength of the healing tendon on day 12. The fact that there were hardly any regulated genes 24 h after loading suggests that optimal stimulation of healing requires a mechanical loading stimulus every day.

Place, publisher, year, edition, pages
AMER PHYSIOLOGICAL SOC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA, 2012
Keywords
Gene expression, tendons, healing
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-70773 (URN)10.1152/japplphysiol.00858.2011 (DOI)000299318400006 ()
Note
funding agencies|Board of Research at the Karolinska Institute||Research Committee at the Karolinska Hospital||Swedish Research Council| 2009-6725 |Swedish National Centre for Research in Sports||King Gustaf V and Queen Victoria Free Mason Foundation||Available from: 2011-09-16 Created: 2011-09-16 Last updated: 2017-12-08Bibliographically approved
Agholme, F., Andersson, T., Tengvall, P. & Aspenberg, P. (2012). Local bisphosphonate release versus hydroxyapatite coating for stainless steel screw fixation in rat tibiae. Journal of materials science. Materials in medicine, 23(3), 743-752
Open this publication in new window or tab >>Local bisphosphonate release versus hydroxyapatite coating for stainless steel screw fixation in rat tibiae
2012 (English)In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 23, no 3, p. 743-752Article in journal (Refereed) Published
Abstract [en]

Implant fixation in bone can be improved by a coating that delivers bisphosphonates locally, or by a hydroxyapatite (HA) coating. In this study, we compared these different types of coatings. For mechanical testing, 30 rats were assigned into three groups, and similar screws were implanted bilaterally in the proximal tibiae. The rats received screws that were either uncoated, coated with nano-crystalline hydroxyapatite or coated with a bisphosphonate releasing protein matrix. After 4 weeks, one screw was subjected to pull-out testing, and the contra-lateral one to torsion testing. For morphology, 30 rats were assigned to similar treatment groups, but received only one screw each. Bisphosphonates enhanced the pull-out force by 41% (P = 0.02) compared to controls, HA increased the pull-out force although not significantly. Conversely, HA increased the maximal torque by 64% (P = 0.02). Morphometry showed higher bone volume around bisphosphonate screws in comparison to HA-coated screws (P andlt; 0.001) and controls (P andlt; 0.001). The results suggest that bisphosphonates improve fixation by increasing the amount of surrounding bone, whereas HA mainly improves bone to implant attachment.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-76616 (URN)10.1007/s10856-011-4539-5 (DOI)000301639900014 ()
Note
Funding Agencies|Swedish Research council|2009-6725|BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy at Sahlgrenska Academy, University of Gothenburg||Available from: 2012-04-13 Created: 2012-04-13 Last updated: 2017-12-07
Andersson, T., Eliasson, P., Hammerman, M., Sandberg, O. & Aspenberg, P. (2012). Low-level mechanical stimulation is sufficient to improve tendon healing in rats. Journal of applied physiology, 113(9), 1398-1402
Open this publication in new window or tab >>Low-level mechanical stimulation is sufficient to improve tendon healing in rats
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2012 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 113, no 9, p. 1398-1402Article in journal (Refereed) Published
Abstract [en]

Treatment of tendon injuries often involves immobilization. However, immobilization might not prevent mild involuntary isometric muscle contraction. The effect of weak forces on tendon healing is therefore of clinical interest. Studies of tendon healing with various methods for load reduction in rat Achilles tendon models show a consistent reduction in tendon strength by at least half, compared with voluntary cage activity. Unloading was not complete in any of these models, and the healing tendon was therefore still exposed to mild mechanical stimulation. By reducing the forces acting on the tendon even further, we now studied the effects of this mild stimulation. Rat Achilles tendons were transected and allowed to heal spontaneously under four different loading conditions: 1) normal cage activity; 2) calf muscle paralysis induced by botulinum toxin A (Botox); 3) tail suspension; 4) Botox and tail suspension, combined, to eliminate even mild stimulation. Healing was evaluated by mechanical testing after 8 days. Botox alone and suspension alone both reduced tendon callus size (transverse area), thereby impairing its strength compared with normal cage activity. The combination of Botox and suspension did not further reduce tendon callus size but drastically impaired the material properties of the tendon callus compared with each treatment alone. The peak force was only a fifth of that in the normal cage activity group. The results indicate that also the mild loading that occurs with either Botox or suspension alone stimulates tendon healing. This stimulation appears to affect mainly tissue quality, whereas stronger stimulation also increases callus size.

Place, publisher, year, edition, pages
American Physiological Society, 2012
Keywords
Achilles tendon, mechanical stress, wound healing, hindlimb unloading, immobilization
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85847 (URN)10.1152/japplphysiol.00491.2012 (DOI)000310649200007 ()
Note

Funding Agencies|Swedish Research Council|2009-6725|Linkoping University||Ostergotland County Council||King Gustaf V and Queen Victoria Free Mason Foundation||Swedish National Center for Research in Sports||

Available from: 2012-11-30 Created: 2012-11-30 Last updated: 2018-02-20
Agholme, F., Andersson, T., Tengvall, P. & Aspenberg, P. (2010). A win for bisphosphonates? Comparison between local bisphosphonate release and hydroxyapatite coating for screw fixation in rats in BONE, vol 46, issue , pp S67-S67. In: BONE (pp. S67-S67). Elsevier Science B.V., Amsterdam., 46
Open this publication in new window or tab >>A win for bisphosphonates? Comparison between local bisphosphonate release and hydroxyapatite coating for screw fixation in rats in BONE, vol 46, issue , pp S67-S67
2010 (English)In: BONE, Elsevier Science B.V., Amsterdam. , 2010, Vol. 46, p. S67-S67Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam., 2010
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-56539 (URN)10.1016/j.bone.2010.01.161 (DOI)000276009300159 ()
Available from: 2010-05-21 Created: 2010-05-21 Last updated: 2010-05-21
Schizas, N., Li, J., Andersson, T., Fahlgren, A., Aspenberg, P., Ahmed, M. & W. Ackermann, P. (2010). Compression Therapy Promotes Proliferative Repair during Rat Achilles Tendon Immobilization. Journal of Orthopaedic Research, 28(7), 852-858
Open this publication in new window or tab >>Compression Therapy Promotes Proliferative Repair during Rat Achilles Tendon Immobilization
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2010 (English)In: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 28, no 7, p. 852-858Article in journal (Refereed) Published
Abstract [en]

Achilles tendon ruptures are treated with an initial period of immobilization, which obstructs the healing process partly by a reduction of blood circulation. Intermittent pneumatic compression (IPC) has been proposed to enhance tendon repair by stimulation of blood flow. We hypothesized that daily IPC treatment can counteract the deficits caused by 2 weeks of immobilization post tendon rupture. Forty-eight Sprague-Dawley SD) rats, all subjected to blunt Achilles tendon transection, were divided in three equal groups. Group A was allowed free cage activity, whereas groups B C were immobilized at the operated hindleg. Group C received daily IPC treatment. Two weeks post-rupture the rats were euthanatized and the tendons analyzed with tensile testing and histological assessments of collagen organization and collagen III-LI occurrence. Immobilization significantly reduced maximum force, energy uptake, stiffness, tendon length, transverse area, stress, organized collagen diameter and collagen III-LI occurrence by respectively 80, 75, 77, 22, 47, 65, 49, and 83% compared to free mobilization. IPC treatment improved maximum force 65%, energy 168%, organized collagen diameter 50%, tendon length 25%, and collagen III-LI occurrence 150% compared to immobilization only. The results confirm that immobilization impairs healing after tendon rupture and furthermore demonstrate that IPC-treatment can enhance proliferative tendon repair by counteracting biomechanical and morphological deficits caused by immobilization.

Place, publisher, year, edition, pages
John Wiley and Sons Ltd., 2010
Keywords
tendon injury; immobilization; intermittent pneumatic compression devices; biomechanics; collagen type III
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-58368 (URN)10.1002/jor.21066 (DOI)000278654500003 ()
Available from: 2010-08-13 Created: 2010-08-11 Last updated: 2017-12-12
Andersson, T., Agholme, F., Aspenberg, P. & Tengvall, P. (2010). Surface immobilized zoledronate improves screw fixation in rat bone: A new method for the coating of metal implants. JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 21(11), 3029-3037
Open this publication in new window or tab >>Surface immobilized zoledronate improves screw fixation in rat bone: A new method for the coating of metal implants
2010 (English)In: JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, ISSN 0957-4530, Vol. 21, no 11, p. 3029-3037Article in journal (Refereed) Published
Abstract [en]

Previous studies show that surface immobilized bisphosphonates improve the fixation of stainless steel screws in rat tibia after 2-8 weeks of implantation. We report here about the immobilization of a potent bisphosphonate, zoledronate, to crosslinked fibrinogen by the use of another technique, i.e. ethyl-dimethyl-aminopropylcarbodiimide (EDC)/imidazole immobilization. Bone fixation of zoledronate-coated screws was compared to screws coated with crosslinked fibrinogen only and ditto with EDC/N-hydroxy-succinimide immobilized pamidronate. Fixation in rat tibia was evaluated by a pull-out test at either 2 or 6 weeks after implantation. Both bisphosphonate coatings increased the pull-out force at both time points, and zoledronate showed a significantly higher pull-out force than pamidronate. To further evaluate the new coating technique we also performed a morphometric study, focusing on the area surrounding the implant. The zoledronate coating resulted in an increased bone density around the screws compared to controls. No pronounced increase was seen around the pamidronate coated screws. Together, the results demonstrate the possibility of obtaining a significant local therapeutic effect with minute amounts of surface immobilized zoledronate.

Place, publisher, year, edition, pages
Springer Science Business Media, 2010
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-63148 (URN)10.1007/s10856-010-4154-x (DOI)000284074500014 ()
Note
The original publication is available at www.springerlink.com: Therese Andersson, Fredrik Agholme, Per Aspenberg and Pentti Tengvall, Surface immobilized zoledronate improves screw fixation in rat bone: A new method for the coating of metal implants, 2010, JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, (21), 11, 3029-3037. http://dx.doi.org/10.1007/s10856-010-4154-x Copyright: Springer Science Business Media http://www.springerlink.com/ Available from: 2010-12-13 Created: 2010-12-13 Last updated: 2010-12-30
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