Arthritis and Physical Treatment

  • Sun, Hui (Herb) (PI)

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant): The long-term objectives of this proposal
are to elucidate the effects of mechanical stimuli to tissue degradation of
rheumatoid arthritis and to develop a physical treatment for relieving pain and
stiffness of arthritic joints. Using two human synovial cell cultures isolated
from rheumatoid arthritis patients, we have recently found that mechanical
shearing at a few dyn/cm 2 transiently decreases the transcriptional levels of
matrix metalloproteinase (MMP)-1, MMP-13 genes as well as ets-1 transcription
factor, while the same shearing increases the mRNA levels of tissue inhibitor
of metalloproteinase (TIMP)-1, TIMP-2 and c-fos. These preliminary gene
expression results suggest a potential use of mechanical shear stress as a
therapeutic tool and allow us to test the following hypothesis: An appropriate
non-stationary temporal profile of gentle mechanical shear stress at a few
dyn/cm2 can maintain simultaneously a reduced mRNA level of MMP-1, 3, and -13
as well as an increased mRNA level of TIMP-1 and 2 through the down-regulation
of ets-1 transcription factor.
Two specific aims of this project are (i) to evaluate the proposed five
non-stationary shear stress profiles for decreasing MMP rRNAs and increasing
TIMP mRNAs, and (ii) to identify the function of ets-1 on mechanical
stress-induced response in the simultaneous regulation of MMPs and TIMPs. We
will isolate RNA from the stress-treated synovial cell cultures and determine
the cDNAs levels of the specific MMPs and TIMPs as well as AP-1 and ets gene
family members using a reverse transcription-polymerase chain reaction
procedure. We will also measure the level of MMP proteins by immunoblotting and
determine MMP activities by using zymography and a fibril degradation assay. By
transfecting ets-1, we will test the function of ets-1 under mechanical
stimuli. The proposed project will contribute to answer whether a non-invasive
physical treatment can be developed for preventing from tissue degradation in
arthritis joints.
StatusFinished
Effective start/end date8/15/027/31/07

ASJC

  • Medicine(all)