Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling
(2013) In FASEB Journal 27(7). p.2687-2701- Abstract
- 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 M. 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 M), and E-64 (IC50 3 M), also inhibited... (More)
- 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 M. 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 M), and E-64 (IC50 3 M), 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, IB, 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. Stralberg, F., Henning, P., Gjertsson, I., Kindlund, B-., Souza, P. P. C., Persson, E., Abrahamson, M., Kasprzykowski, F., Grubb, A., Lerner, U. H. Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4261743
- author
- Stralberg, Fredrik ; Henning, Petra ; Gjertsson, Inger ; Kindlund, Bert ; Souza, Pedro P. C. ; Persson, Emma ; Abrahamson, Magnus LU ; Kasprzykowski, Franciszek ; Grubb, Anders LU and Lerner, Ulf H.
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cystatin C, osteoclasts, Nfatc1, c-Fos
- in
- FASEB Journal
- volume
- 27
- issue
- 7
- pages
- 2687 - 2701
- publisher
- Wiley
- external identifiers
-
- wos:000328841000018
- scopus:84879637850
- pmid:23572233
- ISSN
- 1530-6860
- DOI
- 10.1096/fj.12-211748
- language
- English
- LU publication?
- yes
- id
- f1620448-5d62-4167-897b-8cbc8d9748ad (old id 4261743)
- date added to LUP
- 2016-04-01 14:16:47
- date last changed
- 2023-09-03 11:55:29
@article{f1620448-5d62-4167-897b-8cbc8d9748ad, abstract = {{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 M. 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 M), and E-64 (IC50 3 M), 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, IB, 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. Stralberg, F., Henning, P., Gjertsson, I., Kindlund, B-., Souza, P. P. C., Persson, E., Abrahamson, M., Kasprzykowski, F., Grubb, A., Lerner, U. H. Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling.}}, author = {{Stralberg, Fredrik and Henning, Petra and Gjertsson, Inger and Kindlund, Bert and Souza, Pedro P. C. and Persson, Emma and Abrahamson, Magnus and Kasprzykowski, Franciszek and Grubb, Anders and Lerner, Ulf H.}}, issn = {{1530-6860}}, keywords = {{cystatin C; osteoclasts; Nfatc1; c-Fos}}, language = {{eng}}, number = {{7}}, pages = {{2687--2701}}, publisher = {{Wiley}}, series = {{FASEB Journal}}, title = {{Cysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling}}, url = {{http://dx.doi.org/10.1096/fj.12-211748}}, doi = {{10.1096/fj.12-211748}}, volume = {{27}}, year = {{2013}}, }