Project 1 - Biomechanical Strain Regulation of Fibroblast Cytokines

  • Standley, Paul R (PI)
  • Downey, Fred (PI)
  • Stoll, Scott (PI)
  • Smith, Michael Lamar (PI)

Project: Research project

Description

Despite many reports of favorable patient outcomes post-osteopathic manipulative treatment (OMT), few data suggest cellular mechanisms responsible. In states benefited by OMT, initial strain-induced perturbation of the myofascial (MF) system is suspected to underlie tissue edema, fibrosis, pain, decreased range of motion, and reduced quality of life. MF dysfunction includes alterations in fibroblast-derived cytokine and extracellular matrix proteins (ECMP). Targeted OMTs are designed to normalize tissue strain and consequent MF function. Our new preliminary data shows that acyclic strain of human fibroblasts stimulates fibroblast growth and secretion of IL-6 and nitric oxide (NO). Therefore, we plan to continue to develop and
refine this in vitro cellular model of strain-induced model of injury and OMT in order to study the mechanistic underpinnings of various OMTs. We hypothesize that strain-induced injury of fibroblasts alters IL-6 and NO secretory patterns which are, in turn, responsible for strain-induced alterations in fibroblast growth status and ECMP architecture. Further, we hypothesize that strain designed to simulate OMTs will result in normalization of IL-6 and NO secretion and consequent normalization of fibroblast growth status and ECMP architecture. To test these hypotheses, we will further develop and refine our in vitro system in which cultured human fibroblasts will be mechanically strained and counterstrained in manners simulating injury
and OMT. Then, we will assess potential alterations of IL-6 and NO secretions, fibroblast growth status, and consequent ECMP architecture. We will accomplish this by the following specific aims: 1) We will test various clinically relevant strain and counterstrain magnitudes, frequencies and durations in order to refine our preliminary working in vitro fibroblast model for myofascial injury and effects of OMT simulated counterstrains. 2) We will investigate whether the strain paradigms derived in (1) predictably alter IL-6 and NO expression / secretion, fibroblast proliferation and apoptosis, and the magnitude and/or type of ECMP protein expression / secretion and architecture. This aim will include the critical test of whether subsequent
counterstrain, designed to mimic OMT, reciprocally modulate these variables. 3) We will then attempt to ascribe causative roles for IL-6 and NO in the responses observed in (2) by blocking their biological activities and re-assessing the physiological endpoints.
StatusFinished
Effective start/end date9/1/048/31/10

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Osteopathic Manipulation
Fibroblasts
Cytokines
Extracellular Matrix Proteins
Interleukin-6
Nitric Oxide
Growth
Wounds and Injuries
Articular Range of Motion
Edema
Fibrosis
Quality of Life
Apoptosis
Pain

ASJC

  • Medicine(all)