| Texto completo | |
| Autor(es): |
Teixeira, Jorge F. Lima
;
Henning, Petra
;
Magalhaes, Fernando A. Cintra
;
Coletto-Nunes, Glaucia
;
Floriano-Marcelino, Thais
;
Westerlund, Anna
;
Moverare-Skrtic, Sofia
;
Oliveira, Guilherme J. P. L.
;
Lerner, Ulf H.
;
Souza, Pedro Paulo C.
Número total de Autores: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | CYTOKINE; v. 172, p. 9-pg., 2023-10-26. |
| Resumo | |
Lipoproteins are immunostimulatory bacterial components suggested to participate in inflammation-induced bone loss in periodontal disease through stimulation of osteoclast differentiation. Toll-like receptor 2 activation by Pam2CSK4 (PAM2), known to mimic bacterial lipoproteins, was previously shown to enhance periodontal bone resorption in mice. The anti-inflammatory cytokine interleukin-4 (IL-4) is a known inhibitor of RANKL-induced bone resorption in vitro. Here, we have investigated whether IL-4 could decrease PAM2induced periodontal bone loss and osteoclastogenesis in vivo. In a model of periodontitis induced by gingival injections of PAM2 in mice, concomitant injections of IL-4 reduced bone loss. Histologically, IL-4 reduced the recruitment of inflammatory cells and the formation of TRAP+ osteoclasts stimulated by PAM2. Mouse bone marrow macrophages (BMMs) and neonatal calvarial osteoblasts were used to assess the effect of IL-4 on PAM2induced osteoclastogenesis in vitro. In RANKL-primed BMMs stimulated by PAM2 Nfatc1, Ctsk, and Acp5 gene expression was up-regulated and resulted in robust formation of TRAP+ multinucleated osteoclasts, effects which were impaired by IL-4. These effects were mediated by impairment in PAM2-induced c-fos expression. In primary calvarial osteoblast cultures, IL-4 decreased PAM2-induced Tnfsf11 (encoding RANKL) mRNA and enhanced Tnfrsf11b (encoding OPG) expression. Our data demonstrate that the osteoprotective effect by IL-4 on lipoprotein-induced periodontal disease occurs through the inhibition of osteoclastogenesis by three mechanisms, one by acting directly on osteoclast progenitors, another by acting indirectly through decreasing the expression of osteoclast-regulating cytokines in osteoblasts and a third by decreasing inflammation. (AU) | |
| Processo FAPESP: | 14/05283-3 - Influência da bradicinina sobre a osteoclastogênese in vitro e sobre a reabsorção óssea induzida por LPS in vivo |
| Beneficiário: | Pedro Paulo Chaves de Souza |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |