Efeito de um curcumin modificado quimicamente sobre a reabsorção óssea inflamatória e apoptose: estudos in vivo e in vitro

• Autor(a) principal: Curylofo, Fabiana de Almeida [UNESP]
• Data de Publicação: 2014
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://hdl.handle.net/11449/113932
• topic: Periodontia; Reabsorção óssea; Doenças periodontais; Periodontics

Curcumin (diferuloylmethane) is a polyphenolic compound with anti-inflammatory properties and the ability to prevent the osteolytic activity both in vitro and in vivo models. The clinical use of curcumin is limited by its poor pharmacological properties, including absorption and bioavailability. This justifies the interest on the synthesis of curcumin analogues with improved pharmacological properties that retain both safety and biological properties of the natural compound. The aim was to evaluate the effect of a curcumin synthetic analogue (CMC 2.24) on RANKL-induced osteoclastogenesis in vitro and on inflammatory-driven bone resorption in a periodontal disease model in vivo. Periodontal disease was induced in rats by injections of LPS from Escherichia coli (30 ug/injection) directly on the gingival tissues, performed 3x/week during 2 weeks. The opposite site (controls) received injections of the same volume of vehicle (PBS). CMC (30 mg/kg) and curcumin (100 mg/kg) were administered by oral gavage daily, during this 2 week experimental period. Tartrate resistant acid phosphatase (TRAP) expression, which is indicative of osteoclast differentiation was assessed by immunohistochemistry, bone resorption was measured by microCT and the proportion of inflammatory cells and collagen was assessed by stereometry on H/E-stained section. Apoptosis was assessed in the gingival tissues and alveolar bone by TUNEL staining. Bone marrow stromal cells from C56Bl/7 mice were stimulated with RANKL in the presence of M-CSF and treated with 10 μM of curcumin or CMC 2.24 at different time points over a 6- day period. The number of the osteoclasts identified by actin-ring formation was counted and gene expression of MMP-9, indicative of osteoclast activity, was assessed by RT-qPCR. Both curcumin and CMC significantly reduced the inflammatory infiltrate (p<0.05 vs vehicle control); however only CMC significantly increased the proportion of collagen fibers in...