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, 279-288 p.Article in journal (Refereed) Published
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. Vol. 112, no 2, 279-288 p.
Gene expression, tendons, healing
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-70773DOI: 10.1152/japplphysiol.00858.2011ISI: 000299318400006OAI: oai:DiVA.org:liu-70773DiVA: diva2:441500
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||2011-09-162011-09-162012-03-27Bibliographically approved