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

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorStral̊berg, Fredrik
dc.creatorHenning, Petra
dc.creatorGjertsson, Inger
dc.creatorKindlund, Bert
dc.creatorSouza, Pedro P. C.
dc.creatorPersson, Emma
dc.creatorAbrahamson, Magnus
dc.creatorKasprzykowski, Franciszek
dc.creatorGrubb, Anders
dc.creatorLerner, Ulf H.
dc.date2014-05-27T11:29:49Z
dc.date2016-10-25T18:50:34Z
dc.date2014-05-27T11:29:49Z
dc.date2016-10-25T18:50:34Z
dc.date2013-07-01
dc.date.accessioned2017-04-06T02:28:56Z
dc.date.available2017-04-06T02:28:56Z
dc.identifierFASEB Journal, v. 27, n. 7, p. 2687-2701, 2013.
dc.identifier1530-6860
dc.identifierhttp://hdl.handle.net/11449/75797
dc.identifierhttp://acervodigital.unesp.br/handle/11449/75797
dc.identifier10.1096/fj.12-211748
dc.identifier2-s2.0-84879637850
dc.identifierhttp://dx.doi.org/10.1096/fj.12-211748
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/896529
dc.descriptionThe 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.
dc.languageeng
dc.relationFASEB Journal
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectc-Fos
dc.subjectCystatin C
dc.subjectNfatc1
dc.subjectOsteoclasts
dc.subjectCD14 antigen
dc.subjectcystatin C
dc.subjectcystatin d
dc.subjectcysteine proteinase inhibitor
dc.subjectI kappa B kinase alpha
dc.subjectmessenger RNA
dc.subjectosteoclast differentiation factor
dc.subjectprotein c fos
dc.subjectsynaptotagmin I
dc.subjecttranscription factor NFAT
dc.subjecttranscription factor NFATc1
dc.subjectunclassified drug
dc.subjectanimal cell
dc.subjectapoptosis
dc.subjectbone marrow cell
dc.subjectcell culture
dc.subjectcell differentiation
dc.subjectcell proliferation
dc.subjectcontrolled study
dc.subjectgene expression
dc.subjectmacrophage
dc.subjectmolecular mechanics
dc.subjectmonocyte
dc.subjectnonhuman
dc.subjectosteoclastogenesis
dc.subjectosteolysis
dc.subjectphagocytosis
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectsignal transduction
dc.subjectosteoclasts
dc.subjectAnimals
dc.subjectAntigens, CD14
dc.subjectBlotting, Western
dc.subjectBone Marrow Cells
dc.subjectCell Differentiation
dc.subjectCells, Cultured
dc.subjectCysteine Proteinase Inhibitors
dc.subjectGene Expression
dc.subjectHumans
dc.subjectMacrophages
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMonocytes
dc.subjectNFATC Transcription Factors
dc.subjectProto-Oncogene Proteins c-fos
dc.subjectRANK Ligand
dc.subjectReceptor Activator of Nuclear Factor-kappa B
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectSignal Transduction
dc.titleCysteine proteinase inhibitors regulate human and mouse osteoclastogenesis by interfering with RANK signaling
dc.typeOtro


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