Ibuprofen upregulates expressions of matrix metalloproteinase-1, -8, -9, and -13 without affecting expressions of types I and III collagen in tendon cells.
Nonsteroidal antiinflammatory drugs are widely used to treat sports-related tendon injuries or tendinopathy. This study was designed to investigate the effect of ibuprofen on expressions of types I and III collagen, as well as collagen-degrading enzymes including matrix metalloproteinase (MMP)-1, -2, -8, -9, and -13. Rat Achilles tendon cells were treated with ibuprofen and then underwent MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Reverse transcription-polymerase chain reaction was used to evaluate mRNA expressions of types I and III collagen, MMP-1, -2, -8, -9, and -13. Protein expressions of types I and III collagen, MMP-1, -8, and -13 were determined by Western blot analysis. Gelatin zymography was used to evaluate the enzymatic activities of MMP-2 and MMP-9. The results revealed that ibuprofen upregulated expressions of MMP-1, -8, -9, and -13, both at mRNA and protein levels. There was no effect of ibuprofen on mRNA and protein expressions of types I and III collagen. Gelatin zymography revealed that the enzymatic activity of MMP-9 was upregulated after ibuprofen treatment. In conclusion, ibuprofen upregulates the expressions of collagenases including MMP-1, -8, -9, and -13 without affecting the expressions of types I and III collagen. These findings suggest a molecular mechanism potentially accounting for the inhibition of tendon healing by ibuprofen.
Tsai
Wen-Chung
WC
Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital College of Medicine, Chang Gung University, 5 Fu-Shin Street, Taoyuan County 333, Taiwan.
Hsu
Chih-Chin
CC
Chang
Hsiang-Ning
HN
Lin
Yu-Chun
YC
Lin
Miao-Sui
MS
Pang
Jong-Hwei S
JH
D000125:Achilles Tendon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015153:Blotting, Western; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics* / Q000378:metabolism; D004396:Coloring Agents / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D015870:Gene Expression / Q000187:drug effects; D007052:Ibuprofen / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D024042:Collagen Type I; D024061:Collagen Type III; D004396:Coloring Agents; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D020782:Matrix Metalloproteinases; C022616:thiazolyl blue; D007052:Ibuprofen