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13.03.2024 | Original Article

Intraarticular monomethyl fumarate as a perspective therapy for osteoarthritis by macrophage polarization

verfasst von: Douglas Menezes de Souza, Kauê Franco Malange, Catarine Massucato Nishijima, Bruno Henrique de Melo Lima, Vinicius Cooper Capetini, Alexandre L. R. de Oliveira, Gabriel Forato Anhê, Claudia Herrera Tambeli, Carlos Amilcar Parada

Erschienen in: Inflammopharmacology | Ausgabe 2/2024

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Abstract

Background

Osteoarthritis (OA) is a chronic disease that may lead to joint structure degeneration, cartilage destruction, osteophyte formation, subchondral bone disruption, and pain. In this scenario, a higher proportion of the proinflammatory macrophage type 1 (M1) than the anti-inflammatory macrophage type 2 (M2) could be highlighted as a hallmark of OA progression. The balance between these two macrophage types emerges as a new therapeutic target in OA. This study aimed to evaluate the analgesia and macrophage profile in the treatment of experimental osteoarthritis (EOA) with systemic dimethyl fumarate (DMF) or local intra-articular monomethyl fumarate (MMF).

Results

DMF via gavage or MMF via intra-articular in the right knee of EOA rats showed improvements in gait parameters and the nociceptive recovery of the mechanical threshold assessment by adapted electronic von Frey treatment on the twenty-first day (long-lasting phase). DMF treatment decreased proinflammatory TNF-α while increasing anti-inflammatory IL-10 cytokines from the macerated capsule on the fifth day (inflammatory phase). MMF treatment showed joint capsule mRNA extraction downregulating iNOS and TNF-α gene expression while upregulating IL-10 and MCP-1. However, CD206 was not significant but higher than untreated EOA rats’ joints on the seventh day (inflammatory phase).

Conclusions

Our studies with EOA model induced by MIA suggest a new perspective for human treatment committed with OA based on macrophage polarization as a therapeutic target, switching the proinflammatory profile M1 to the anti-inflammatory profile M2 with DMF systematic or by MMF locally treatment according to the OA severity.

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Titel: Intraarticular monomethyl fumarate as a perspective therapy for osteoarthritis by macrophage polarization
verfasst von: Douglas Menezes de Souza
Kauê Franco Malange
Catarine Massucato Nishijima
Bruno Henrique de Melo Lima
Vinicius Cooper Capetini
Alexandre L. R. de Oliveira
Gabriel Forato Anhê
Claudia Herrera Tambeli
Carlos Amilcar Parada
Publikationsdatum: 13.03.2024
Verlag: Springer International Publishing
Erschienen in: Inflammopharmacology / Ausgabe 2/2024
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-024-01443-w

Springer Medizin

Abstract

Background

Results

Conclusions

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