Optimizing an intermittent stretch paradigm using ERK1/2 phosphorylation results in increased collagen synthesis in engineered ligaments

Jennifer Z. Paxton, Paul Hagerty, Jonathan J. Andrick, Keith Baar

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Dynamic mechanical input is believed to play a critical role in the development of functional musculoskeletal tissues. To study this phenomenon, cyclic uniaxial mechanical stretch was applied to engineered ligaments using a custom-built bioreactor and the effects of different stretch frequency, amplitude, and duration were determined. Stretch acutely increased the phosphorylation of p38 (3.5±0.74-fold), S6K1 (3.9±0.19-fold), and ERK1/2 (2.45±0.32-fold). The phosphorylation of ERK1/2 was dependent on time, rather than on frequency or amplitude, within these constructs. ERK1/2 phosphorylation was similar following stretch at frequencies from 0.1 to 1 Hz and amplitudes from 2.5% to 15%, whereas phosphorylation reached maximal levels at 10 min of stretch and returned toward basal within 60 min of stretch. Following a single 10-min bout of cyclic stretch, the cells remained refractory to a second stretch for up to 6 h. Using the phosphorylation of ERK1/2 as a guide, the optimum stretch paradigm was hypothesized to be 10 min of stretch at 2.5% of resting length repeated every 6 h. Consistent with this hypothesis, 7 days of stretch using this optimized intermittent stretch program increased the collagen content of the grafts more than a continuous stretch program (CTL=3.1%±0.44%; CONT=4.8%±0.30%; and INT=5.9%±0.56%). These results suggest that short infrequent bouts of loading are optimal for improving engineered tendon and ligament physiology.

Original languageEnglish (US)
Pages (from-to)277-284
Number of pages8
JournalTissue Engineering - Part A
Volume18
Issue number3-4
DOIs
StatePublished - Feb 1 2012

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Phosphorylation
Ligaments
Collagen
Musculoskeletal Development
Tendons
Physiology
Bioreactors
Grafts
Refractory materials
Tissue
Transplants

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials
  • Medicine(all)

Cite this

Optimizing an intermittent stretch paradigm using ERK1/2 phosphorylation results in increased collagen synthesis in engineered ligaments. / Paxton, Jennifer Z.; Hagerty, Paul; Andrick, Jonathan J.; Baar, Keith.

In: Tissue Engineering - Part A, Vol. 18, No. 3-4, 01.02.2012, p. 277-284.

Research output: Contribution to journalArticle

Paxton, Jennifer Z. ; Hagerty, Paul ; Andrick, Jonathan J. ; Baar, Keith. / Optimizing an intermittent stretch paradigm using ERK1/2 phosphorylation results in increased collagen synthesis in engineered ligaments. In: Tissue Engineering - Part A. 2012 ; Vol. 18, No. 3-4. pp. 277-284.
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