Otro
Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling
Registro en:
FASEB Journal, v. 27, n. 7, p. 2687-2701, 2013.
1530-6860
10.1096/fj.12-211748
2-s2.0-84879637850
Autor
Stral̊berg, Fredrik
Henning, Petra
Gjertsson, Inger
Kindlund, Bert
Souza, Pedro P. C.
Persson, Emma
Abrahamson, Magnus
Kasprzykowski, Franciszek
Grubb, Anders
Lerner, Ulf H.
Resumen
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.
Materias
Ítems relacionados
Mostrando ítems relacionados por Título, autor o materia.
-
Diseases, injuries, and risk factors in child and adolescent health, 1990 to 2017 findings from the global burden of diseases, injuries, and risk factors 2017 study
Robert C., Reiner Jr; Olsen, Helen Elizabeth; Ikeda, Chad Thomas; Echko, Michelle M.; Ballestreros, Katherine E.; Manguerra, Helen; Martopullo, Ira; Millear, Anoushka; Shields, Chloe; Alvis-Guzman, Nelson