Importance of Strain Direction in Regulating Human Fibroblast Proliferation and Cytokine Secretion

A Useful in Vitro Model for Soft Tissue Injury and Manual Medicine Treatments

Thomas S. Eagan, Kate R. Meltzer, Paul R Standley

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Objective: Manual medicine treatments (MMTs) rely on biophysical techniques that use manually guided forces in numerous strain directions to treat injuries and somatic dysfunctions. Although clinical outcomes post-MMT are positive, the underlying cellular mechanisms responsible remain elusive. We previously described an in vitro model of strain-induced tissue injury and MMTs. Using this model, the current study sought to determine if strain direction (equibiaxial [EQUI] vs heterobiaxial [HETERO]) differentially regulates human fibroblast function. Methods: Fibroblasts were strained EQUI at 10% beyond their resting length for 48 hours followed by assessment of cell morphology, proliferation, and cytokine secretion via protein cytokine array and enzyme-linked immunosorbent assay (ELISA). These observations were then compared with those obtained previously for HETERO fibroblasts. Results: No alterations in cell morphology were seen in EQUI fibroblasts despite our report of such changes in HETERO cells. Fibroblasts secretion profiles for 60 cytokines (via cytokine protein array) showed that in EQUI strained cells, fractalkine significantly increased (121%), whereas macrophage-derived chemoattractant/chemokine and pulmonary and activation-regulated chemokine significantly decreased (32% and 10%, respectively) compared with nonstrained cells (P < .05). The EQUI fibroblasts when compared with HETERO fibroblasts exhibited a significant decrease in proliferation (22%), inflammatory interleukin 6 secretion (75%, measured by ELISA), and macrophage-derived chemoattractant/chemokine secretion (177%, measured by ELISA, P < .05). Conclusions: These divergent observations in HETERO vs EQUI strained fibroblasts may underlie the relative efficacies of MMTs carried out in different tissue strain directions. We are currently modeling MMTs such as myofascial release to further investigate this.

Original languageEnglish (US)
Pages (from-to)584-592
Number of pages9
JournalJournal of Manipulative and Physiological Therapeutics
Volume30
Issue number8
DOIs
StatePublished - Oct 2007

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Soft Tissue Injuries
Fibroblasts
Medicine
Cytokines
Chemokine CCL22
Protein Array Analysis
Enzyme-Linked Immunosorbent Assay
Chemotactic Factors
Therapeutics
Chemokine CX3CL1
Direction compound
In Vitro Techniques
Wounds and Injuries
Chemokines
Interleukin-6
Cell Proliferation
Lung

Keywords

  • Cytokines
  • Fibroblast
  • Manual Therapies
  • Soft Tissue Injuries
  • Strain

ASJC Scopus subject areas

  • Physical Therapy, Sports Therapy and Rehabilitation
  • Health Professions(all)
  • Nursing(all)

Cite this

@article{5803228d761e4899ac2f319aaaf24637,
title = "Importance of Strain Direction in Regulating Human Fibroblast Proliferation and Cytokine Secretion: A Useful in Vitro Model for Soft Tissue Injury and Manual Medicine Treatments",
abstract = "Objective: Manual medicine treatments (MMTs) rely on biophysical techniques that use manually guided forces in numerous strain directions to treat injuries and somatic dysfunctions. Although clinical outcomes post-MMT are positive, the underlying cellular mechanisms responsible remain elusive. We previously described an in vitro model of strain-induced tissue injury and MMTs. Using this model, the current study sought to determine if strain direction (equibiaxial [EQUI] vs heterobiaxial [HETERO]) differentially regulates human fibroblast function. Methods: Fibroblasts were strained EQUI at 10{\%} beyond their resting length for 48 hours followed by assessment of cell morphology, proliferation, and cytokine secretion via protein cytokine array and enzyme-linked immunosorbent assay (ELISA). These observations were then compared with those obtained previously for HETERO fibroblasts. Results: No alterations in cell morphology were seen in EQUI fibroblasts despite our report of such changes in HETERO cells. Fibroblasts secretion profiles for 60 cytokines (via cytokine protein array) showed that in EQUI strained cells, fractalkine significantly increased (121{\%}), whereas macrophage-derived chemoattractant/chemokine and pulmonary and activation-regulated chemokine significantly decreased (32{\%} and 10{\%}, respectively) compared with nonstrained cells (P < .05). The EQUI fibroblasts when compared with HETERO fibroblasts exhibited a significant decrease in proliferation (22{\%}), inflammatory interleukin 6 secretion (75{\%}, measured by ELISA), and macrophage-derived chemoattractant/chemokine secretion (177{\%}, measured by ELISA, P < .05). Conclusions: These divergent observations in HETERO vs EQUI strained fibroblasts may underlie the relative efficacies of MMTs carried out in different tissue strain directions. We are currently modeling MMTs such as myofascial release to further investigate this.",
keywords = "Cytokines, Fibroblast, Manual Therapies, Soft Tissue Injuries, Strain",
author = "Eagan, {Thomas S.} and Meltzer, {Kate R.} and Standley, {Paul R}",
year = "2007",
month = "10",
doi = "10.1016/j.jmpt.2007.07.013",
language = "English (US)",
volume = "30",
pages = "584--592",
journal = "Journal of Manipulative and Physiological Therapeutics",
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TY - JOUR

T1 - Importance of Strain Direction in Regulating Human Fibroblast Proliferation and Cytokine Secretion

T2 - A Useful in Vitro Model for Soft Tissue Injury and Manual Medicine Treatments

AU - Eagan, Thomas S.

AU - Meltzer, Kate R.

AU - Standley, Paul R

PY - 2007/10

Y1 - 2007/10

N2 - Objective: Manual medicine treatments (MMTs) rely on biophysical techniques that use manually guided forces in numerous strain directions to treat injuries and somatic dysfunctions. Although clinical outcomes post-MMT are positive, the underlying cellular mechanisms responsible remain elusive. We previously described an in vitro model of strain-induced tissue injury and MMTs. Using this model, the current study sought to determine if strain direction (equibiaxial [EQUI] vs heterobiaxial [HETERO]) differentially regulates human fibroblast function. Methods: Fibroblasts were strained EQUI at 10% beyond their resting length for 48 hours followed by assessment of cell morphology, proliferation, and cytokine secretion via protein cytokine array and enzyme-linked immunosorbent assay (ELISA). These observations were then compared with those obtained previously for HETERO fibroblasts. Results: No alterations in cell morphology were seen in EQUI fibroblasts despite our report of such changes in HETERO cells. Fibroblasts secretion profiles for 60 cytokines (via cytokine protein array) showed that in EQUI strained cells, fractalkine significantly increased (121%), whereas macrophage-derived chemoattractant/chemokine and pulmonary and activation-regulated chemokine significantly decreased (32% and 10%, respectively) compared with nonstrained cells (P < .05). The EQUI fibroblasts when compared with HETERO fibroblasts exhibited a significant decrease in proliferation (22%), inflammatory interleukin 6 secretion (75%, measured by ELISA), and macrophage-derived chemoattractant/chemokine secretion (177%, measured by ELISA, P < .05). Conclusions: These divergent observations in HETERO vs EQUI strained fibroblasts may underlie the relative efficacies of MMTs carried out in different tissue strain directions. We are currently modeling MMTs such as myofascial release to further investigate this.

AB - Objective: Manual medicine treatments (MMTs) rely on biophysical techniques that use manually guided forces in numerous strain directions to treat injuries and somatic dysfunctions. Although clinical outcomes post-MMT are positive, the underlying cellular mechanisms responsible remain elusive. We previously described an in vitro model of strain-induced tissue injury and MMTs. Using this model, the current study sought to determine if strain direction (equibiaxial [EQUI] vs heterobiaxial [HETERO]) differentially regulates human fibroblast function. Methods: Fibroblasts were strained EQUI at 10% beyond their resting length for 48 hours followed by assessment of cell morphology, proliferation, and cytokine secretion via protein cytokine array and enzyme-linked immunosorbent assay (ELISA). These observations were then compared with those obtained previously for HETERO fibroblasts. Results: No alterations in cell morphology were seen in EQUI fibroblasts despite our report of such changes in HETERO cells. Fibroblasts secretion profiles for 60 cytokines (via cytokine protein array) showed that in EQUI strained cells, fractalkine significantly increased (121%), whereas macrophage-derived chemoattractant/chemokine and pulmonary and activation-regulated chemokine significantly decreased (32% and 10%, respectively) compared with nonstrained cells (P < .05). The EQUI fibroblasts when compared with HETERO fibroblasts exhibited a significant decrease in proliferation (22%), inflammatory interleukin 6 secretion (75%, measured by ELISA), and macrophage-derived chemoattractant/chemokine secretion (177%, measured by ELISA, P < .05). Conclusions: These divergent observations in HETERO vs EQUI strained fibroblasts may underlie the relative efficacies of MMTs carried out in different tissue strain directions. We are currently modeling MMTs such as myofascial release to further investigate this.

KW - Cytokines

KW - Fibroblast

KW - Manual Therapies

KW - Soft Tissue Injuries

KW - Strain

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DO - 10.1016/j.jmpt.2007.07.013

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JF - Journal of Manipulative and Physiological Therapeutics

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