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Different gene response to mechanical loading during early and late phases of rat Achilles tendon healing.
- Source :
-
Journal of applied physiology (Bethesda, Md. : 1985) [J Appl Physiol (1985)] 2017 Oct 01; Vol. 123 (4), pp. 800-815. Date of Electronic Publication: 2017 Jul 13. - Publication Year :
- 2017
-
Abstract
- Mechanical loading stimulates tendon healing both when applied in the inflammatory phase and in the early remodeling phase of the process, although not necessarily via the same mechanisms. We investigated the gene response to mechanical loading in these two phases of tendon healing. The right Achilles tendon in rats was transected, and the hindlimbs were unloaded by tail suspension. The rats were exposed to 5 min of treadmill running 3 or 14 days after tendon transection. Thereafter, they were resuspended for 15 min or 3 h until euthanasia. The controls were suspended continuously. Gene analysis was first performed by microarray analysis followed by quantitative RT-PCR on selected genes, focusing on inflammation. Fifteen minutes after loading, the most important genes seemed to be the transcription factors EGR1 and C-FOS, regardless of healing phase. These transcription factors might promote tendon cell proliferation and differentiation, stimulate collagen production, and regulate inflammation. Three hours after loading on day 3 , inflammation was strongly affected. Seven inflammation-related genes were upregulated according to PCR: CCL20, CCL7, IL-6, NFIL3, PTX3, SOCS1, and TLR2. These genes can be connected to macrophages, T cells, and recruitment of leukocytes. According to Ingenuity Pathway Analysis, the recruitment of leukocytes was increased by loading on day 3 , which also was confirmed by histology. This inflammation-related gene response was not seen on day 14 Our results suggest that the immediate gene response after mechanical loading is similar in the early and late phases of healing but the late gene response is different. NEW & NOTEWORTHY This study investigates the direct effect of mechanical loading on gene expression during different healing phases in tendon healing. One isolated episode of mechanical loading was studied in otherwise unloaded healing tendons. This enabled us to study a time sequence, i.e., which genes were the first ones to be regulated after the loading episode.<br /> (Copyright © 2017 the American Physiological Society.)
- Subjects :
- Animals
Early Growth Response Protein 1 metabolism
Female
Gene Expression Regulation
Hindlimb Suspension
Inflammation genetics
Proto-Oncogene Proteins c-fos metabolism
Rats, Sprague-Dawley
Running
Tendon Injuries genetics
Achilles Tendon metabolism
Inflammation metabolism
Physical Conditioning, Animal
Tendon Injuries metabolism
Wound Healing
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1601
- Volume :
- 123
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of applied physiology (Bethesda, Md. : 1985)
- Publication Type :
- Academic Journal
- Accession number :
- 28705996
- Full Text :
- https://doi.org/10.1152/japplphysiol.00323.2017