TY - JOUR
T1 - Messenger-RNA expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases, and transcription factors in rheumatic synovial cells under mechanical stimuli
AU - Sun, H. B.
AU - Yokota, H.
N1 - Funding Information:
The authors thank Drs. James McAteer for valuable suggestions. This work was in part supported by NIH NIAMS (AR20582-22).
PY - 2001
Y1 - 2001
N2 - In an effort to elucidate the role of mechanical stimuli in rheumatoid arthritis, we determined mRNA levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, and three transcription factors (c-fos, ets-1, and ets-2) under two mechanical shearing conditions as well as simulated unloading. Human synovial cell cultures (MH7A and RA99-01), derived from rheumatoid arthritis patients, were grown for 1 h under mechanical stimuli and the transcript level was assayed by the reverse transcription-polymerase-chain reaction procedure. First, gentle shearing, estimated at ∼1 dyn/cm2, induced a consistent decrease in mRNA level of MMP-1, MMP-3, MMP-13, and ets-1 and an increase in the transcript level of TIMP-1, TIMP-2, c-fos, and ets-2. Second, intermediate shearing, estimated at ∼6 dyn/cm2, elevated the mRNA level of all MMPs, TIMPs, and the three transcription factors. Third, minimum mRNA level of c-fos, ets-1, and ets-2 was achieved under control conditions at rest, gentle shearing, and simulated unloading, respectively. These in vitro results support a stimulus-dependent transcriptional regulation of MMPs, TIMPs, and transcription factors in cell cultures, suggesting a potential role of shear stress in tissue degradation and prevention in rheumatic joints.
AB - In an effort to elucidate the role of mechanical stimuli in rheumatoid arthritis, we determined mRNA levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, and three transcription factors (c-fos, ets-1, and ets-2) under two mechanical shearing conditions as well as simulated unloading. Human synovial cell cultures (MH7A and RA99-01), derived from rheumatoid arthritis patients, were grown for 1 h under mechanical stimuli and the transcript level was assayed by the reverse transcription-polymerase-chain reaction procedure. First, gentle shearing, estimated at ∼1 dyn/cm2, induced a consistent decrease in mRNA level of MMP-1, MMP-3, MMP-13, and ets-1 and an increase in the transcript level of TIMP-1, TIMP-2, c-fos, and ets-2. Second, intermediate shearing, estimated at ∼6 dyn/cm2, elevated the mRNA level of all MMPs, TIMPs, and the three transcription factors. Third, minimum mRNA level of c-fos, ets-1, and ets-2 was achieved under control conditions at rest, gentle shearing, and simulated unloading, respectively. These in vitro results support a stimulus-dependent transcriptional regulation of MMPs, TIMPs, and transcription factors in cell cultures, suggesting a potential role of shear stress in tissue degradation and prevention in rheumatic joints.
KW - Human synovial cells
KW - Matrix metalloproteinase (MMP)
KW - Mechanical stimuli
KW - Rheumatoid arthritis (RA)
KW - Tissue inhibitor of metalloproteinase (TIMP)
KW - c-fos
KW - ets-1
KW - ets-2
UR - http://www.scopus.com/inward/record.url?scp=0035119612&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035119612&partnerID=8YFLogxK
U2 - 10.1016/S8756-3282(00)00454-3
DO - 10.1016/S8756-3282(00)00454-3
M3 - Article
C2 - 11248661
AN - SCOPUS:0035119612
SN - 8756-3282
VL - 28
SP - 303
EP - 309
JO - Bone
JF - Bone
IS - 3
ER -