RRC ID 68003
Author Sun HB, Yokota H.
Title Messenger-RNA expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases, and transcription factors in rheumatic synovial cells under mechanical stimuli.
Journal Bone
Abstract 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 approximately 1 dyn/cm(2), 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 approximately 6 dyn/cm(2), 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.
Volume 28(3)
Pages 303-9
Published 2001-3-1
DOI 10.1016/s8756-3282(00)00454-3
PII S8756-3282(00)00454-3
PMID 11248661
MeSH Arthritis, Rheumatoid / genetics* Arthritis, Rheumatoid / pathology Base Sequence Cells, Cultured DNA Primers Down-Regulation Gelatinases / metabolism Humans Matrix Metalloproteinases / genetics* Physical Stimulation* RNA, Messenger / genetics* Reverse Transcriptase Polymerase Chain Reaction Synovial Membrane / cytology Synovial Membrane / enzymology Synovial Membrane / metabolism* Tissue Inhibitor of Metalloproteinase-1 / genetics* Tissue Inhibitor of Metalloproteinase-2 / genetics* Transcription Factors / genetics*
Human and Animal Cells MH7A(RCB1512)