L J Moilanen1, M Hämäläinen2, E Nummenmaa3, P Ilmarinen4, K Vuolteenaho5, R M Nieminen6, L Lehtimäki7, E Moilanen8. 1. The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: lauri.j.moilanen@uta.fi. 2. The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: mari.j.hamalainen@uta.fi. 3. The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: elina.nummenmaa@uta.fi. 4. The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: pinja.ilmarinen@uta.fi. 5. The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: katriina.vuolteenaho@uta.fi. 6. The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: riina.m.nieminen@uta.fi. 7. The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: lauri.lehtimaki@uta.fi. 8. The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: eeva.moilanen@uta.fi.
Abstract
OBJECTIVES: 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. 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. 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. 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.
OBJECTIVES: 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. 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 mousecartilage. 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. 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.
Authors: Stefan Heber; Markus Gold-Binder; Cosmin I Ciotu; Martin Witek; Nino Ninidze; Hans-Georg Kress; Michael J M Fischer Journal: J Neurosci Date: 2019-03-12 Impact factor: 6.167
Authors: Patrick Kanju; Yong Chen; Whasil Lee; Michele Yeo; Suk Hee Lee; Joelle Romac; Rafiq Shahid; Ping Fan; David M Gooden; Sidney A Simon; Ivan Spasojevic; Robert A Mook; Rodger A Liddle; Farshid Guilak; Wolfgang B Liedtke Journal: Sci Rep Date: 2016-06-01 Impact factor: 4.379
Authors: Elina Nummenmaa; Mari Hämäläinen; Lauri J Moilanen; Erja-Leena Paukkeri; Riina M Nieminen; Teemu Moilanen; Katriina Vuolteenaho; Eeva Moilanen Journal: Arthritis Res Ther Date: 2016-08-11 Impact factor: 5.156