Utilize este identificador para referenciar este registo: http://hdl.handle.net/10362/13804
Título: Osteoclast activity in ankylosing spondylitis patients before and after TNF-blocking therapy
Autor: Raposeiro, Rita Maria Mendes
Orientador: Lopes, Joana
Perpétuo, Inês
Palavras-chave: Ankylosing spondylitis
Inflammation
Osteoclastogenesis
TNF-blocking therapy
Data de Defesa: Out-2014
Resumo: Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease of the axial skeleton. The major outcome of this disease is defined by new bone formation, commonly observed in the ligaments of the intervertebral joints, that can lead to the formation of bony spurs, known as syndesmophytes. Previous studies have shown that serum levels of TNF, IL-6 and IL-17 are increased in AS patients and may be implicated in the development of secondary osteoporosis, since these cytokines are able to induce osteoclast (OC) differentiation and, therefore, bone resorption. In this work we aimed to assess the effects of TNF-blocking therapy in the systemic inflammatory environment of AS patients with active disease as well as in OC differentiation and activity. To accomplish this objective, we cultured circulating monocytes from AS patients, before and after therapy, under osteoclastogenic conditions and we performed two functional assays (TRAP staining and resorption pit assay) and analyzed the expression of osteoclast specific genes. We have shown that AS patients with active disease have increased levels of pro-inflammatory cytokines when compared with healthy subjects. We also found that IL-17, TGF-β and osteoprotegerin are decreased after TNF-blocking therapy. Interestingly, we also observed that after TNF-blocking therapy the expression of some genes is favoring osteoclastogenesis and that differentiated OCs have increased resorption activity. These results suggest that in active AS there may be an uncoupling between inflammation and OC activity that is reset by TNF-blocking therapy.
URI: http://hdl.handle.net/10362/13804
Designação: Dissertação
Aparece nas colecções:FCT: DCV - Dissertações de Mestrado

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