Role of TLR4 activation and signaling in bone remodeling, and afferent sprouting in serum transfer arthritis

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AudienciaPúblico en generales_ES
CoberturaMéxicoes_ES
Fecha de ingreso2026-10-05T16:33:18Z
Fecha de publicación2024-01-01
ResumenBackgroundIn the murine K/BxN serum transfer rheumatoid arthritis (RA) model, tactile allodynia persists after resolution of inflammation in male and partially in female wild type (WT) mice, which is absent in Toll-like receptor (TLR)4 deficient animals. We assessed the role of TLR4 on allodynia, bone remodeling and afferent sprouting in this model of arthritis.MethodsK/BxN sera were injected into male and female mice with conditional or stable TLR4 deletion and controls. Paw swelling was scored and allodynia assessed by von Frey filaments. At day 28, synovial neural fibers were visualized with confocal microscopy and bone density assayed with microCT. Microglial activity and TLR4 dimerization in spinal cords were examined by immunofluorescence and flow cytometry.ResultsIn the synovium, K/BxN injected WT male and female mice showed robust increases in calcitonin gene related-peptide (CGRP+), tyrosine hydroxylase (TH)+ and GAP43+ nerve fibers. Trabecular bone density by microCT was significantly decreased in K/BxN WT female but not in WT male mice. The number of osteoclasts increased in both sexes of WT mice, but not in Tlr4-/- K/BxN mice. We used conditional strains with Cre drivers for monocytes/osteoclasts (lysozyme M), microglia (Tmem119 and Cx3CR1), astrocytes (GFAP) and sensory neurons (advillin) for Tlr4f/f disruption. All strains developed similar arthritis scores after K/BxN serum injection with the exception being the Tlr4Tmem119 mice which showed a reduction. Both sexes of Tlr4Lyz2, Tlr4Tmem119 and Tlr4Cx3cr1 mice displayed a partial reversal of the chronic pain phenotype but not in Tlr4Avil, and Tlr4Gfap mice. WT K/BxN male mice showed increases in spinal Iba1, but not GFAP, compared to Tlr4-/- male mice. To determine whether spinal TLR4 was indeed activated in the K/BxN mice, flow cytometry of lumbar spinal cords of WT K/BxN male mice was performed and revealed that TLR4 in microglia cells (CD11b+ /TMEM119+) demonstrated dimerization (e.g. activation) and a characteristic increase in lipid rafts.ConclusionThese results demonstrated a complex chronic allodynia phenotype associated with TLR4 in microglia and monocytic cell lineages, and a parallel spinal TLR4 activation. However, TLR4 is dispensable for the development of peripheral nerve sprouting in this model.es_ES
Doihttps://doi.org/10.1186/s13075-024-03424-4es_ES
URIhttps://riuat.uat.edu.mx/handle/123456789/5131
Idiomaenes_ES
EditorialBMCes_ES
RelaciónArthritis Research and Therapyes_ES
URL relacionadohttps://doi.org/10.1186/s13075-024-03424-4es_ES
DerechosAcceso abierto (Metadatos de producción científica)es_ES
Licenciahttp://purl.org/coar/access_right/c_abf2es_ES
FuenteArthritis Research and Therapy
Palabra clavePaines_ES
Palabra claveArthritises_ES
Palabra claveTLR4es_ES
Palabra claveMicrogliaes_ES
Palabra claveInflammationes_ES
Palabra claveCGRPes_ES
TítuloRole of TLR4 activation and signaling in bone remodeling, and afferent sprouting in serum transfer arthritises_ES
TipoArtículoes_ES
ArbitradoHa sido Arbitradoes_ES
Autordos Santos, Gilson Goncalves
AutorJimenez-Andrade, Juan Miguel
AutorMunoz-Islas, Enriqueta
AutorCandanedo-Quiroz, Mariana E.
AutorCardenas, Andrea Gonzalez
AutorDrummond, Bronwen
AutorPham, Peter
AutorStilson, Gwendalynn
AutorHsu, Chao-Chin
AutorDelay, Lauriane
AutorNavia-Pelaez, Juliana M.
AutorLemes, Julia Paes
AutorMiller, Yury I.
AutorYaksh, Tony L.
AutorCorr, Maripat
Autordos Santos, Gilson Goncalveses_ES
AutorJimenez-Andrade, Juan Migueles_ES
AutorMunoz-Islas, Enriquetaes_ES
AutorCandanedo-Quiroz, Mariana E.es_ES
AutorCardenas, Andrea Gonzalezes_ES
AutorDrummond, Bronwenes_ES
AutorPham, Peteres_ES
AutorStilson, Gwendalynnes_ES
AutorHsu, Chao-Chines_ES
AutorDelay, Laurianees_ES
AutorNavia-Pelaez, Juliana M.es_ES
AutorLemes, Julia Paeses_ES
AutorMiller, Yury I.es_ES
AutorYaksh, Tony L.es_ES
AutorCorr, Maripates_ES
InstituciónUniversidad Autónoma de Tamaulipas
InstituciónUniversidad Autónoma de Tamaulipases_ES
Número1es_ES
URL relacionadahttps://doi.org/10.1186/s13075-024-03424-4
Tipo de artículoIndexado
Tipo de artículoIndexadoes_ES
Volumen26es_ES

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