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Provedor de dados:  BJMBR
País:  Brazil
Título:  Adenovirus-mediated siRNA targeting TNF-α and overexpression of bone morphogenetic protein-2 promotes early osteoblast differentiation on a cell model of Ti particle-induced inflammatory response in vitro
Autores:  Guo,H.H.
Yu,C.C.
Sun,S.X.
Ma,X.J.
Yang,X.C.
Sun,K.N.
Jin,Q.H.
Data:  2013-10-01
Ano:  2013
Palavras-chave:  TNF-α
BMP-2
Small interfering RNA
Titanium particles
Osteolysis
Resumo:  Wear particles are phagocytosed by macrophages and other inflammatory cells, resulting in cellular activation and release of proinflammatory factors, which cause periprosthetic osteolysis and subsequent aseptic loosening, the most common causes of total joint arthroplasty failure. During this pathological process, tumor necrosis factor-alpha (TNF-α) plays an important role in wear-particle-induced osteolysis. In this study, recombination adenovirus (Ad) vectors carrying both target genes [TNF-α small interfering RNA (TNF-α-siRNA) and bone morphogenetic protein 2 (BMP-2)] were synthesized and transfected into RAW264.7 macrophages and pro-osteoblastic MC3T3-E1 cells, respectively. The target gene BMP-2, expressed on pro-osteoblastic MC3T3-E1 cells and silenced by the TNF-α gene on cells, was treated with titanium (Ti) particles that were assessed by real-time PCR and Western blot. We showed that recombinant adenovirus (Ad-siTNFα-BMP-2) can induce osteoblast differentiation when treated with conditioned medium (CM) containing RAW264.7 macrophages challenged with a combination of Ti particles and Ad-siTNFα-BMP-2 (Ti-ad CM) assessed by alkaline phosphatase activity. The receptor activator of nuclear factor-κB ligand was downregulated in pro-osteoblastic MC3T3-E1 cells treated with Ti-ad CM in comparison with conditioned medium of RAW264.7 macrophages challenged with Ti particles (Ti CM). We suggest that Ad-siTNFα-BMP-2 induced osteoblast differentiation and inhibited osteoclastogenesis on a cell model of a Ti particle-induced inflammatory response, which may provide a novel approach for the treatment of periprosthetic osteolysis.
Tipo:  Info:eu-repo/semantics/article
Idioma:  Inglês
Identificador:  http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2013001000831
Editor:  Associação Brasileira de Divulgação Científica
Relação:  10.1590/1414-431X20133092
Formato:  text/html
Fonte:  Brazilian Journal of Medical and Biological Research v.46 n.10 2013
Direitos:  info:eu-repo/semantics/openAccess
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