Ibuprofen upregulates expressions of matrix metalloproteinase-1, -8, -9, and -13 without affecting expressions of types I and III collagen in tendon cells

Abstract

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. ß

The Detrimental Effects of Systemic Ibuprofen Delivery on Tendon Healing Are Time-Dependent

“…This could suggest either that structural reorganization of the healing tendon is altered due to early ibuprofen administration or that earlier matrix degradation and production are altered by ibuprofen administration. NSAIDs have been shown to alter both cell motility and tenocyte matrix metalloproteinase expression in vitro [30,31], lending support to these ideas. Interestingly, the delayed group did exhibit a recovery of fiber alignment with increased postsurgery time, but this process seemed delayed as there was no significant difference between 1 and 2 weeks postsurgery, as in the control.…”

The Achilles Tendinopathy: Pathogenesis Review

“…For what concern corticosteroids injections there are several case reports [90,91] of tendon rupture after their use in patients while animal studies have shown that they lead to a reduction in tendon strength [92] , but these findings are not universal and there is a lack of goodquality research data to support their use in tendinopathy [93] . Nonsteroidal anti-inflammatory drugs (NSAIDs) are shown to modulate tendon cell proliferation, the expression of extracellular matrix components and degenerative enzymes [94,95] . As their use is common for sport-related symptoms, it is possible that they contribute to the development of tendinopathy [96] .…”

Low‐level laser therapy in collagenase‐induced Achilles tendinitis in rats: Analyses of biochemical and biomechanical aspects

“…2 Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed and used to treat tendon injuries over the years. 5 However, these drugs usually treat only the symptoms of inflammation and not the disease cause. 4,6 Additionally, it has been observed several kinds of side effects related to long-term use of these drugs.…”

“…1,9 Furthermore, very few is known about cellular changes related to this increased risk, 1 but it has been hypothesized that some pharmacological treatments are harmful to tendon due to up-regulate expressions of matrix metalloproteinases (MMPs) such as MMP-9 and MMP-13. 5 MMPs play an important role in tendon matrix morphology, it degrades collagen and proteoglycans in healthy and sickness conditions. 10 The tendon matrix remodeling is related directly to balance between MMPs and their inhibitors.…”