Inhibition of matrix metalloproteinase-9 activity by doxycycline ameliorates RANK ligand-induced osteoclast differentiation in vitro and in vivo

dc.creatorFranco, GCN
dc.creatorKajiya, M
dc.creatorNakanishi, T
dc.creatorOhta, K
dc.creatorRosalen, PL
dc.creatorGroppo, FC
dc.creatorErnst, CWO
dc.creatorBoyesen, JL
dc.creatorBartlett, JD
dc.creatorStashenko, P
dc.creatorTaubman, MA
dc.creatorKawai, T
dc.date2011
dc.date40330
dc.date2014-08-01T18:32:55Z
dc.date2015-11-26T17:03:45Z
dc.date2014-08-01T18:32:55Z
dc.date2015-11-26T17:03:45Z
dc.date.accessioned2018-03-28T23:51:56Z
dc.date.available2018-03-28T23:51:56Z
dc.identifierExperimental Cell Research. Elsevier Inc, v. 317, n. 10, n. 1454, n. 1464, 2011.
dc.identifier0014-4827
dc.identifierWOS:000291184800012
dc.identifier10.1016/j.yexcr.2011.03.014
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/80588
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/80588
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1279165
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionTetracycline antibiotics, including doxycycli\e (DOX), have been used to treat bone resorptive diseases, partially because of their activity to suppress osteoclastogenesis induced by receptor activator of nuclear factor kappa B ligand (RANKL). However, their precise inhibitory mechanism remains unclear. Therefore, the present study examined the effect of Dox on osteoclastogenesis signaling induced by RANKL, both in vitro and in vivo. Although Dox inhibited RANKL-induced osteoclastogenesis and down-modulated the mRNA expression, of functional osteoclast markers, including tartrate-resistant acid phosphatase (TRAP) and cathepsin K. Dox neither affected RANKL-induced MAPKs phosphorylation nor NFATc1 gene expression in RAW264.7 murine monocytic cells. Gelatin zymography and Western blot analyses showed that Dox down-regulated the enzyme activity of RANKL-induced MMP-9, but without affecting its protein expression. Furthermore, MMP-9 enzyme inhibitor also attenuated both RANKL-induced osteoclastogenesis and up-regulation of TRAP and cathepsin K mRNA expression, indicating that MMP-9 enzyme action is engaged in the promotion of RANKL-induced osteoclastogenesis. Finally, Dox treatment abrogated RANKL-induced osteoclastogenesis and TRAP activity in mouse calvaria along with the suppression of MMP9 enzyme activity, again without affecting the expression of MMP9 protein. These findings suggested that Dox inhibits RANKL-induced osteoclastogenesis by its inhibitory effect on MMP-9 enzyme activity independent of the MAPK-NFATc1 signaling cascade. (C) 2011 Elsevier Inc. All rights reserved.
dc.description317
dc.description10
dc.description1454
dc.description1464
dc.descriptionNIDCR [DE-016276, DE-03420, DE-09018, DE-14551, DE-18499, DE-19917]
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionNIDCR [DE-016276, DE-03420, DE-09018, DE-14551, DE-18499, DE-19917]
dc.descriptionFAPESP [05/54580]
dc.languageen
dc.publisherElsevier Inc
dc.publisherSan Diego
dc.publisherEUA
dc.relationExperimental Cell Research
dc.relationExp. Cell Res.
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjectDoxycycline
dc.subjectOsteoclast
dc.subjectRANK ligand
dc.subjectMMP-9
dc.subjectMAPKs
dc.subjectNFATc1
dc.subjectPeriodontal-disease
dc.subjectBone-resorption
dc.subjectMatrix Metalloproteinases
dc.subjectAdult Periodontitis
dc.subjectMembrane-proteins
dc.subjectGene-expression
dc.subjectLong Bones
dc.subjectTetracyclines
dc.subjectActivation
dc.subjectMarrow
dc.titleInhibition of matrix metalloproteinase-9 activity by doxycycline ameliorates RANK ligand-induced osteoclast differentiation in vitro and in vivo
dc.typeArtículos de revistas


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