Dopamine delays articular cartilage degradation in osteoarthritis by negative regulation of the NF-?B and JAK2/STAT3 signaling pathways - 01/10/19
, Junting Ma b, ⁎ , Zongsheng Yin a, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
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Graphical abstract |
The chondroprotective effects of dopamine on osteoarthritis were possibly related to its ability to inhibit the NF-κB and JAK2/STAT3 signaling pathways.
Highlights |
• | Dopamine suppressed matrix-degrading protease production in OA chondrocytes. |
• | Dopamine reduced the activation of the NF-κB pathway induced by IL-1β. |
• | Dopamine exhibits chondroprotective effects by inhibiting the JAK2/STAT3 pathway activation. |
• | Dopamine prevented the development of osteoarthritis in a mouse model. |
Abstract |
Background |
The progressive loss of cartilage matrix and the breakdown of articular cartilage induced by inflammation play an essential role in osteoarthritis (OA) pathogenesis. Dopamine (DA) is a critical neurotransmitter that is not only involved in controlling exercise, emotion, cognition and neuroendocrine activity but also has anti-inflammatory effects. This study aimed to investigate the effects of DA on OA in vitro and in vivo.
Methods |
OA progression was evaluated in a mouse model with surgically induced destabilization of the medial meniscus. Cartilage degradation and OA were analyzed using Safranin O/Fast Green staining. Additionally, qRT-PCR and Western blotting were applied to detect catabolic and anabolic factors involved in cartilage degeneration and underlying mechanisms in OA chondrocytes treated with Interleukin-1β.
Results |
In vitro, DA treatment inhibited the production of inducible nitric oxide synthase, cyclooxygenase-2, matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13, while increasing type II collagen and glycosaminoglycan content. Mechanistically, DA reversed IL-1β-treated nuclear factor-kappa B activation and JAK2/STAT3 phosphorylation. Furthermore, DA suppressed the degradation of cartilage matrix and reduced Osteoarthritis Research Society International scores in the surgically induced OA models.
Conclusion |
DA may be a novel therapeutic agent for OA treatment.
Le texte complet de cet article est disponible en PDF.Abbreviations : OA, DA, DMM, iNOS, COX-2, MMP, GAGs, NF-κB, NO, PGE2, ECM, IL-1β, IL-6, TNF-α, NSAIDs, OARSI, JAK2, STAT3
Keywords : Osteoarthritis, Dopamine, NF-κB, JAK2/STAT3, Chondrocytes
Plan
Vol 119
Article 109419- novembre 2019 Retour au numéro
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