Monosodium iodoacetate-induced inflammation and joint pain are reduced in TRPA1 deficient mice - potential role of TRPA1 in osteoarthritis

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• 作者：L.J. Moilanen ^{lauri.j.moilanen@uta.fi" class="auth_mail" title="E-mail the corresponding author} ; M. Hä ; mä ; lä ; inen ^{mari.j.hamalainen@uta.fi" class="auth_mail" title="E-mail the corresponding author} ; E. Nummenmaa ^{elina.nummenmaa@uta.fi" class="auth_mail" title="E-mail the corresponding author} ; P. Ilmarinen ^{pinja.ilmarinen@uta.fi" class="auth_mail" title="E-mail the corresponding author} ; K. Vuolteenaho ^{katriina.vuolteenaho@uta.fi" class="auth_mail" title="E-mail the corresponding author} ; R.M. Nieminen ^{riina.m.nieminen@uta.fi" class="auth_mail" title="E-mail the corresponding author} ; L. Lehtimä ; ki ^{lauri.lehtimaki@uta.fi" class="auth_mail" title="E-mail the corresponding author} ; E. Moilanen ; ^{eeva.moilanen@uta.fi" class="auth_mail" title="E-mail the corresponding author}
• 关键词：TRPA1 ; Monosodium iodoacetate-induced osteoarthritis ; Inflammation ; Joint pain ; COX-2
• 刊名：Osteoarthritis and Cartilage
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：23
• 期：11
• 页码：2017-2026
• 全文大小：976 K

文摘

Intra-articularly injected monosodium iodoacetate (MIA) induces joint pathology mimicking osteoarthritis (OA) and it is a widely used experimental model of OA. MIA induces acute inflammation, cartilage degradation and joint pain. Transient Receptor Potential Ankyrin 1 (TRPA1) is an ion channel known to mediate nociception and neurogenic inflammation. Here, we tested the hypothesis that TRPA1 would be involved in the development of MIA-induced acute inflammation, cartilage changes and joint pain.

ec_2">Methods

The effects of pharmacological blockade (by TCS 5861528) and genetic depletion of TRPA1 were studied in MIA-induced acute paw inflammation. Cartilage changes (histological scoring) and joint pain (weight-bearing test) in MIA-induced experimental OA were compared between wild type and TRPA1 deficient mice. The effects of MIA were also studied in primary human OA chondrocytes and in mouse cartilage.

ec_3">Results

MIA evoked acute inflammation, degenerative cartilage changes and joint pain in wild type mice. Interestingly, these responses were attenuated in TRPA1 deficient animals. MIA-induced paw inflammation was associated with increased tissue levels of substance P; and the inflammatory edema was reduced by pretreatment with catalase, with the TRPA1 antagonist TCS 5861528 and with the neurokinin 1 receptor antagonist L703,606. In chondrocytes, MIA enhanced interleukin-1 induced cyclooxygenase-2 (COX-2) expression, an effect that was blunted by pharmacological inhibition and genetic depletion of TRPA1.

ec_4">Conclusions

TRPA1 was found to mediate acute inflammation and the development of degenerative cartilage changes and joint pain in MIA-induced experimental OA in the mouse. The results reveal TRPA1 as a potential mediator and drug target in OA.