| Full text | |
| Author(s): Show less - |
Schneider, Ayda Henriques
;
Taira, Thaise Mayumi
;
Publio, Gabriel Azevedo
;
Prado, Douglas da Silva
;
Yabuta, Paula Barbim Donate
;
dos Santos, Jessica Cristina
;
Machado, Caio Cavalcante
;
de Souza, Flavio Falcao Lima
;
Venturini, Lucas Gabriel Rodrigues
;
de Oliveira, Rene Donizeti Ribeiro
;
Cunha, Thiago Mattar
;
Alves-Filho, Jose Carlos
;
Louzada-Junior, Paulo
;
da Silva, Tarcilia Aparecida
;
Fukada, Sandra Yasuyo
;
Cunha, Fernando Queiroz
Total Authors: 16
|
| Document type: | Journal article |
| Source: | British Journal of Pharmacology; v. N/A, p. 18-pg., 2023-09-28. |
| Abstract | |
Background and PurposeRheumatoid arthritis (RA) is a chronic autoimmune disease that can cause bone erosion due to increased osteoclastogenesis. Neutrophils involvement in osteoclastogenesis remains uncertain. Given that neutrophil extracellular traps (NETs) can act as inflammatory mediators in rheumatoid arthritis, we investigated the role of NETs in stimulating bone loss by potentiating osteoclastogenesis during arthritis.Experimental ApproachThe level of NETs in synovial fluid from arthritis patients was assessed. Bone loss was evaluated by histology and micro-CT in antigen-induced arthritis (AIA)-induced WT mice treated with DNase or in Padi4-deficient mice (Padi4flox/flox LysMCRE). The size and function of osteoclasts and the levels of RANKL and osteoprotegerin (OPG) released by osteoblasts that were incubated with NETs were measured. The expression of osteoclastogenic marker genes and protein levels were evaluated by qPCR and western blotting. To assess the participation of TLR4 and TLR9 in osteoclastogenesis, cells from Tlr4-/- and Tlr9-/- mice were cultured with NETs.Key ResultsRheumatoid arthritis patients had higher levels of NETs in synovial fluid than osteoarthritis patients, which correlated with increased levels of RANKL/OPG. Moreover, patients with bone erosion had higher levels of NETs. Inhibiting NETs with DNase or Padi4 deletion alleviated bone loss in arthritic mice. Consistently, NETs enhanced RANKL-induced osteoclastogenesis that was dependent on TLR4 and TLR9 and increased osteoclast resorptive functions in vitro. In addition, NETs stimulated the release of RANKL and inhibited osteoprotegerin in osteoblasts, favouring osteoclastogenesis.Conclusions and ImplicationsInhibiting NETs could be an alternative strategy to reduce bone erosion in arthritis patients. image (AU) | |
| FAPESP's process: | 13/08216-2 - CRID - Center for Research in Inflammatory Diseases |
| Grantee: | Fernando de Queiroz Cunha |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 19/19190-0 - Role of NETs as osteoclastogenesis modulators in Rheumatoid Arthritis |
| Grantee: | Ayda Henriques Schneider |
| Support Opportunities: | Scholarships in Brazil - Doctorate |