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J Physiol. 2015 Oct 15;593(20):4665-75. doi: 10.1113/JP270737. Epub 2015 Sep 14.

The exercise-induced biochemical milieu enhances collagen content and tensile strength of engineered ligaments.

Author information

1
Department of Physiology and Membrane Biology, University of California Davis, One Shields Ave, Davis, CA, 95616, USA.
2
Department of Biomedical Engineering, University of California Davis, One Shields Ave, Davis, CA, 95616, USA.
3
Department of Neurobiology, Physiology and Behaviour, University of California Davis, One Shields Ave, Davis, CA, 95616, USA.
4
Department of Orthopaedic Surgery, University of California Davis, One Shields Ave, Davis, CA, 95616, USA.

Abstract

Exercise stimulates a dramatic change in the concentration of circulating hormones, such as growth hormone (GH), but the biological functions of this response are unclear. Pharmacological GH administration stimulates collagen synthesis; however, whether the post-exercise systemic milieu has a similar action is unknown. We aimed to determine whether the collagen content and tensile strength of tissue-engineered ligaments is enhanced by serum obtained post-exercise. Primary cells from a human anterior cruciate ligament (ACL) were used to engineer ligament constructs in vitro. Blood obtained from 12 healthy young men 15 min after resistance exercise contained GH concentrations that were ∼7-fold greater than resting serum (P < 0.001), whereas IGF-1 was not elevated at this time point (P = 0.21 vs. rest). Ligament constructs were treated for 7 days with medium supplemented with serum obtained at rest (RestTx) or 15 min post-exercise (ExTx), before tensile testing and collagen content analysis. Compared with RestTx, ExTx enhanced collagen content (+19%; 181 ± 33 vs. 215 ± 40 μg per construct P = 0.001) and ligament mechanical properties - maximal tensile load (+17%, P = 0.03 vs. RestTx) and ultimate tensile strength (+10%, P = 0.15 vs. RestTx). In a separate set of engineered ligaments, recombinant IGF-1, but not GH, enhanced collagen content and mechanics. Bioassays in 2D culture revealed that acute treatment with post-exercise serum activated mTORC1 and ERK1/2. In conclusion, the post-exercise biochemical milieu, but not recombinant GH, enhances collagen content and tensile strength of engineered ligaments, in association with mTORC1 and ERK1/2 activation.

PMID:
26282066
PMCID:
PMC4606526
DOI:
10.1113/JP270737
[Indexed for MEDLINE]
Free PMC Article

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