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Mechanical Loading Effects on Human
Osteoarthritic Cartilage
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Principal Investigator: R. Lane Smith, PhD
Collaborators: Gary S. Beaupré, PhD; Dennis R. Carter, PhD;
Nicholas J. Giori, MD, PhD; Stuart B. Goodman, MD, PhD; Andrew R. Hoffman, MD;
William J. Maloney, MD; David J. Schurman, MD; and John C. Zauner, MD
Objective: Osteoarthritis remains a major health problem for veterans
and the general population at large. The long-term goal of this research
program is to develop fundamental knowledge regarding articular cartilage
responses to mechanical loading as a means for improving treatment.
Specific Aims
Specific Aim 1: Application of intermittent hydrostatic pressure at a
physiologically relevant loading level will increase the synthesis and
deposition in osteoarthritic articular cartilage samples.
Specific Aim 2: Addition of BMP-2 will induce an added stimulation of
matrix production in the presence of applied physiologically relevant loading
levels of intermittent hydrostatic pressure.
Progress during 2006
- Obtained a functional hand-held cartilage stiffness measuring device and
set up initial testing protocols for determination of osteochondral samples
possessing full-thickness articular cartilage surface layer
- Established a minimally invasive and low-heat generating cutting system for
the removal of excess subchondral bone from osteochondral samples of
osteoarthritic cartilage
- Applied intermittent hydrostatic pressure to full-thickness articular
cartilage samples maintained in defined serum-free culture medium in the
presence and absence of added BMP-2 for duration of 10 weeks with a culture
medium change after 5 weeks of loading. Samples were run from two patients in
multiples of five replicates for each test condition.
- Examined the genetic responsiveness of high density monolayer cultures of
isolated osteoarthritic articular chondrocytes in high density monolayer
culture following exposure to intermittent hydrostatic pressure in the presence
and absence of added BMP-2 in a defined serum-free culture medium.
Main Findings
- BMP-2 provides an additional stimulus to that of intermittent hydrostatic
pressure for increased signal levels for mRNA for cartilage matrix
macromolecules, aggrecan and type II collagen. The delivery of the BMP-2 is
critically dependent on the presence of carrier protein in the growth factor
preparation; carrier free BMP-2 did not show a similar level of efficacy,
presumable due to loss on the cartilage culture vessel surfaces.
Plan for Subsequent Years
- Increase the number of patient specific samples treated with BMP-2 with the
addition of intermittent hydrostatic pressure.
- Expand the mechanical testing regimen to include cartilage stiffness using
the handheld indenter with compressive modulus determination at the termination
of the loading regimens.
- Add a normal cartilage trial to the experimental analysis of the effects of
BMP-2 and intermittent hydrostatic pressure on cartilage matrix mechanical
properties.
- Expand the analysis of genetic responsiveness to the cartilage extractable
proteome using 2-D gel analysis coupled with mass-spectroscopy for protein
identification and quantification.
- Complete two manuscripts describing the isolated chondrocyte responsiveness
to mechanical loading.
Published Abstracts
Mawtari T, Lindsey D, Kajiyama G, Suenaga E, Goodman, D, Schurman, D,
Maloney W, Smith RL. Effect of tensile strain/fluid flow on human
osteoarthritic articular cartilage. Trans Orthop Res Soc, 31:1486, 2006
Smith RL, Dhulipala L, Kajiyama G, Goodman S, Maloney W, Schurman D.
Osteoarthritic chondrocyte metabolism: Effects of shear stress on interleukin-6
and nitric oxide synthase expression. Trans Orthop Res Soc, 31:1532,
2006
Ma T, Nelson E, Mawatari T, Oh K, Larsen M, Smith R, Goodman S. Effects of
local infusion of OP-1 on particle or NSAID-mediated bone formation in vivo.
Trans Orthop Res Soc, 31:0688, 2006
Funding Source: Department of Veterans Affairs - Merit Review
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