title: Influence of TNF-α and biomechanical stress on matrix metalloproteinases and lysyl oxidases expressions in human knee synovial fibroblasts.
abstract: OBJECTIVE
  It was reported that not only ACL but also the synovium may be the major regulator of matrix metalloproteinases (MMPs) in synovial fluids after ACL injury. In order to further confirm whether synovium is capable of regulating the microenvironment in the process of ACL injury, the complicated microenvironment of joint cavity after ACL injury was mimicked and the combined effects of mechanical injury and inflammatory factor [tumour necrosis factor-α (TNF-α)] on expressions of lysyl oxidases (LOXs) and MMPs in synovial fibroblasts derived from normal human synovium were studied.
  
  
  METHODS
  Human normal knee joint synovial fibroblasts were stimulated for 1-6 h with mechanical stretch and inflammatory factor (TNF-α). Total RNA was harvested, reverse transcribed and assessed by real-time polymerase chain reaction for the expression of LOXs and MMP-1, 2, 3 messenger RNAs. MMP-2 activity was assayed from the collected culture media samples using zymography.
  
  
  RESULTS
  Compared to control group, our results showed that 6% physiological stretch increased MMP-2 and LOXs (except LOXL-3), decreased MMP-1 and MMP-3; injurious stretch (12%) decreased LOXs (except LOXL-2)and increased MMP-1, 2 and 3; the combination of injurious stretch and TNF-α decreased LOXs and increased MMP-1, 2 and 3 in synovial fibroblasts in a synergistical manner.
  
  
  CONCLUSIONS
  This study demonstrated that combination of mechanical injury and inflammatory factors up-regulated the expressions of MMPs and down-regulated the expressions of LOXs in synovial fibroblasts, eventually alter the balance of tissue healing. Thus, synovium may be involved in regulating the microenvironment of joint cavity. Based on the mechanism, early interventions to inhibit the production of MMPs or promote the production of LOXs in the synovial fibroblasts should be performed to facilitate the healing of tissue.
authors: "111" Project Laboratory of Biomechanics and Tissue Repair, Bioengineering College, Chongqing University, Chongqing, 400044, China.
authors: Yanjun
authors: Y
authors: Zhang
authors: Wei
authors: W
authors: Huang
authors: Jiahuang
authors: J
authors: Jiang
authors: Jing
authors: J
authors: Xie
authors: Chunmin
authors: C
authors: Xu
authors: Chunli
authors: C
authors: Wang
authors: Lin
authors: L
authors: Yin
authors: Li
authors: L
authors: Yang
authors: Kevin
authors: K
authors: Zhou
authors: Peter
authors: P
authors: Chen
authors: Kl Paul
authors: KP
authors: Sung
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007719:Knee Joint / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D008875:Middle Aged; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis*; D012333:RNA, Messenger; D013314:Stress, Mechanical; D013583:Synovial Membrane / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D008249:Protein-Lysine 6-Oxidase; D020782:Matrix Metalloproteinases
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