Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling

The cysteine proteinase inhibitor cystatin C inhibited RANKL-stimulated osteoclast formation in mouse bone marrow macrophage cultures, an effect associated with decreased mRNA expression of Acp5, Calcr, Ctsk, Mmp9, Itgb3, and Atp6i, without effect on proliferation or apoptosis. The effects were concentration dependent with half-maximal inhibition at 0.3 μM. Cystatin C also inhibited osteoclast formation when RANKL-stimulated osteoclasts were cultured on bone, leading to decreased formation of resorption pits. RANKL-stimulated cells retained characteristics of phagocytotic macrophages when cotreated with cystatin C. Three other cysteine proteinase inhibitors, cystatin D, Z-RLVG-CHN2 (IC50 0.1 μM), and E-64 (IC 50 3 μM), also inhibited osteoclast formation in RANKL-stimulated macrophages. In addition, cystatin C, Z-RLVG-CHN2, and E-64 inhibited osteoclastic differentiation of RANKL-stimulated CD14+ human monocytes. The effect by cystatin C on differentiation of bone marrow macrophages was exerted at an early stage after RANKL stimulation and was associated with early (4 h) inhibition of c-Fos expression and decreased protein and nuclear translocation of c-Fos. Subsequently, p52, p65, IκBα, and Nfatc1 mRNA were decreased. Cystatin C was internalized in osteoclast progenitors, a process requiring RANKL stimulation. These data show that cystatin C inhibits osteoclast differentiation and formation by interfering intracellularly with signaling pathways downstream RANK. © FASEB.

The role of cytokines in inflammatory bone loss

Chronic inflammatory processes close to bone often lead to loss of bone in diseases such as rheumatoid arthritis, periodontitis, loosened joint prosthesis and tooth implants. This is mainly due to local formation of bone resorbing osteoclasts which degrade bone without any subsequent coupling to new bone formation. Crucial for osteoclastogenesis is stimulation of mononuclear osteoclast progenitors by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) which induces their differentiation along the osteoclastic lineage and the fusion to mature, multinucleated osteoclasts. M-CSF and RANKL are produced by osteoblasts/ osteocytes and by synovial and periodontal fibroblasts and the expression is regulated by pro- and anti-inflammatory cytokines. These cytokines also regulate osteoclastic differentiation by direct effects on the progenitor cells. In the present overview, we introduce the basic concepts of osteoclast progenitor cell differentiation and summarize the current knowledge on cytokines stimulating and inhibiting osteoclastogenesis by direct and indirect mechanisms. © Informa Healthcare USA, Inc.

Probiótico na alimentação do pacu (Piaractus mesopotamicus): avaliação hematológica, bioquímica, imunológica e desempenho produtivo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito de um treinamento de FNP sobre variáveis biomecânicas em idosos caidores

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cuba: algunos aspectos demograficos de las areas urbana y rural en la provincia de Camaguey

Incluye Bibliografía

Republica Argentina: estimacion y analisis descriptivo de la migracion de la provincia del Neuquen correspondiente al periodo 1965-1970

Incluye Bibliografía

Situación actual y perspectivas de la enseñanza de la demografía en México; versión preliminar

Incluye Bibliografía

Estudos das propriedades estruturais de análogos substituídos com 'TRP POT.2,7 ou 24' do fragmento com 30 resíduos da região amino-terminal da Esticolisina II

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Indicadores de qualidade de um Latossolo Vermelho após onze anos em sistemas de cultivos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

O estado como empregador de última instância: uma abordagem a partir das finanças funcionais

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Distribuição de frequência das condições de céu em função das variações climáticas em Botucatu-SP

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação físico-química de palhiço de cana-de-açúcar utilizado para cogeração de energia elétrica

Pós-graduação em Agronomia (Energia na Agricultura) - FCA

Desempenho ortográfico de escolares do ensino fundamental: elaboração e aplicação de um instrumento de intervenção

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A significação na epistemologia genética: contribuições para uma teoria do conhecimento

Pós-graduação em Filosofia - FFC

Caribbean Documentation Centre: list of serials 1981

Indice de publicaciones periódicas recibidas regularmente en el Centro de Documentación del Caribe hasta fines de 1981.