RESUMO
Gold nanoparticles inhibited osteoclast (OC) formation induced by the receptor activator of nuclear factor-κB ligand (RANKL) in bone marrow-derived macrophages (BMMs). This was accompanied by a decreased level of tartrate-resistant alkaline phosphatase (TRAP) and less activation of nuclear factor (NF)-κB. The nanoparticles also reduced the production of reactive oxygen species (ROS) in response to RANKL and upregulated RANKL-induced glutathione peroxidase-1 (Gpx-1), suggesting a role as an antioxidant in the BMM. The inhibitory effects on OC formation might have been due to elevated defense against oxidative stress.
Assuntos
Antioxidantes , Glutationa Peroxidase/genética , Nanopartículas Metálicas/química , Osteoclastos/citologia , Ligante RANK/antagonistas & inibidores , Receptor Ativador de Fator Nuclear kappa-B/antagonistas & inibidores , Animais , Ouro , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Ligante RANK/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/genética , Glutationa Peroxidase GPX1RESUMO
Obesity induces a low-grade systemic chronic inflammatory condition for which macrophages are responsible. We hypothesized that obesity affects osteoclastogenesis by acting on bone marrow-derived macrophages (BMM). Male mice were fed a high-fat diet (45% of energy) or a standard diet (10% of energy) for 13 wk. We found that the density of the femurs of obese mice was significantly lower than that of the femurs of lean mice. Osteoclastogenesis was enhanced in the BMM from obese mice. Lower levels of interleukin (IL)-10 were generated by the BMM from obese mice than by those from lean mice upon stimulation of receptor activator of nuclear factor-kappaB ligand. Neutralization of IL-10 in the BMM from obese mice was not as effective in increasing osteoclast (OC) formation as that in those from lean mice. Exogenous IL-10 inhibited OC formation more strongly in the BMM from obese mice than those from lean mice. The elevated level of OC formation in the BMM from obese mice may thus be due to in part to the lower level of IL-10, a negative regulator of osteoclastogenesis. Our results suggest that obesity is associated with bone loss via enhanced osteoclastogenesis due to reduced IL-10 production by the BMM from obese mice.
Assuntos
Densidade Óssea/fisiologia , Gorduras na Dieta/administração & dosagem , Macrófagos/fisiologia , Obesidade/metabolismo , Osteoclastos/fisiologia , Animais , Reabsorção Óssea/etiologia , Reabsorção Óssea/metabolismo , Interleucina-10/metabolismo , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/complicações , Ligante RANK/farmacologia , Organismos Livres de Patógenos EspecíficosRESUMO
Curcumin (diferuloylmethane), a pigment derived from turmeric, has anti-oxidant and anti-inflammatory activities. Accumulating evidence points to a biochemical link between increased oxidative stress and reduced bone density. Osteoclast formation was evaluated in co-cultures of bone marrow stromal cells (BMSC) and whole bone marrow cells (BMC). Expression of receptor activator of nuclear factor-kappaB ligand (RANKL) was analyzed at the mRNA and protein levels. Exposure to curcumin led to dose-dependent suppression of osteoclastogenesis in the coculture system, and to reduced expression of RANKL in IL-1alpha-stimulated BMSCs. Addition of RANKL abolished the inhibition of osteoclastogenesis by curcumin, whereas the addition of prostaglandin E2(PGE2) did not. The decreased osteoclastogenesis induced by curcumin may reduce bone loss and be of potential benefit in preventing and/or attenuating osteoporosis.
Assuntos
Células da Medula Óssea/citologia , Curcumina/farmacologia , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ligante RANK/metabolismo , Células Estromais/metabolismo , Animais , Técnicas de Cocultura , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucina-1alfa/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/metabolismo , Ligante RANK/genética , Células Estromais/citologia , Células Estromais/efeitos dos fármacosRESUMO
Rutin, a glycoside of flavonol, inhibits osteoclast formation induced by receptor activator of NF-kappaB ligand (RANKL) in bone marrow-derived macrophages. It reduces reactive oxygen species produced by RANKL and its inhibitory effect results from reduced levels of TNF-alpha. Rutin also lowers NF-kappaB activation in response to RANKL.
Assuntos
NF-kappa B/metabolismo , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Rutina/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Ligante RANK/farmacologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
The oral administration of extracts of young radishes cultivated with sulfur after intravenous tumor cell injection achieved a marked reduction of pulmonary colonization in mice. Treatment of the mice with extracts of young radish cultivated with sulfur did not show any increase in the number of CD8+ or NK T cells in the spleen, indicating no influence on host immunity. Sulforaphane, which could be a candidate for an active compound from young radishes cultivated with sulfur, inhibited cell growth of B16-F10 melanoma cells. In addition, extracts of the young radish cultivated with sulfur-fed group showed enhanced quinine reductase (QR) activities in the liver and lung and a slight increase of glutathione S-transferase (GST) activity in the liver. These results suggested that the administration of extracts of young radishes cultivated with sulfur suppressed pulmonary tumorigenesis, possibly due to increased activity of detoxification enzymes in the liver and lung, and partly due to cell cytotoxicity.