- 作者: Shin-Han Tsai; Ming-Thau Sheu; Yu-Chih Liang; Hsiu-Tan Cheng; Sheng-Shiung Fang; Chien-Ho Chen
- 作者服務機構: Department of Neurosurgery, Department of Emergency and Critical Care Medicine, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
To investigate the mechanism how Transforming growth factor-β (TGF-β) represses
Interleukin-1β(IL-1β)-induced Proteinase-Activated Receptor-2 (PAR-2) expression
in human primary synovial cells (hPSCs). Human chondrocytes and hPSCs isolated
from cartilages and synovium of Osteoarthritis (OA) patients were cultured with
10% fetal bovine serum media or serum free media before treatment with IL-1β,
TGF-β1, or Connective tissue growth factor (CTGF). The expression of PAR-2 was
detected using reverse transcriptase-polymerase chain reaction (RT-PCR) and
western blotting. Collagen zymography was performed to assess the activity of
Matrix metalloproteinases-13 (MMP-13). It was demonstrated that IL-1β induces
PAR-2 expression via p38 pathway in hPSCs. This induction can be repressed by
TGF-β and was observed to persist for at least 48 hrs, suggesting that
TGF-β inhibits PAR-2 expression through multiple pathways. First of all, TGF-β
was able to inhibit PAR-2 activity by inhibiting IL-1β-induced p38 signal
transduction and secondly the inhibition was also indirectly due to MMP-13
inactivation. Finally, TGF-β was able to induce CTGF, and in turn CTGF represses
PAR-2 expression by inhibiting IL-1β-induced phospho-p38 level. TGF-β could
prevent OA from progression with the anabolic ability to induce CTGF production
to maintain extracellular matrix (ECM) integrity and to down regulate PAR-2
expression, and the anti-catabolic ability to induce Tissue inhibitors of
metalloproteinase-3 (TIMP-3) production to inhibit MMPs leading to avoid PAR-2
over-expression. Because IL-1β-induced PAR-2 expressed in hPSCs might play a
significantly important role in early phase of OA, PAR-2 repression by exogenous
TGF-β or other agents might be an ideal therapeutic target to prevent OA from progression. - 中文關鍵字: --
- 英文關鍵字: --