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dc.contributor.authorWinrow, VR
dc.contributor.authorMesher, J
dc.contributor.authorMeghji, S
dc.contributor.authorMorris, CJ
dc.contributor.authorMaguire, M
dc.contributor.authorFox, Simon
dc.contributor.authorCoates, ARM
dc.contributor.authorTormay, P
dc.contributor.authorBlake, DR
dc.contributor.authorHenderson, B
dc.date.accessioned2023-02-15T15:29:14Z
dc.date.available2023-02-15T15:29:14Z
dc.date.issued2008-10
dc.identifier.issn1462-5814
dc.identifier.issn1462-5822
dc.identifier.urihttp://hdl.handle.net/10026.1/20389
dc.description.abstract

Mycobacterium tuberculosis produces two homologous chaperonin (Cpn)60 proteins, Cpn60.1 and Cpn60.2 (Hsp65). Both proteins stimulate human and murine monocyte cytokine synthesis but, unlike Cpn60 proteins from other microbial species, fail to stimulate the breakdown of cultured murine bone. Here, we have examined the mechanism of action of these proteins on bone remodelling and osteoclastogenesis, induced in vitro in murine calvarial explants and the murine monocyte cell line RAW264.7. Additionally, we have determined their effect on bone remodelling in vivo in an animal model of arthritis. Recombinant Cpn60.1 but not Cpn60.2 inhibited bone breakdown both in vitro, in murine calvaria and in vivo, in experimental arthritis. Analysis of the mechanism of action of Cpn60.1 suggests that this protein works by directly blocking the synthesis of the key osteoclast transcription factor, nuclear factor of activated T cells c1. The detection of circulating immunoreactive intact Cpn60.1 in a small number of patients with tuberculosis but not in healthy controls further suggests that the skeleton may be affected in patients with tuberculosis. Taken together, these findings reveal that M. tuberculosis Cpn60.1 is a potent and novel inhibitor of osteoclastogenesis both in vitro and in vivo and a potential cure for bone-resorptive diseases like osteoporosis.

dc.format.extent2091-2104
dc.format.mediumPrint-Electronic
dc.languageen
dc.language.isoeng
dc.publisherHindawi Limited
dc.subjectAnimals
dc.subjectBacterial Proteins
dc.subjectBone Regeneration
dc.subjectCell Differentiation
dc.subjectCell Line
dc.subjectChaperonin 60
dc.subjectMice
dc.subjectMonocytes
dc.subjectMycobacterium tuberculosis
dc.subjectOrgan Culture Techniques
dc.subjectOsteoclasts
dc.titleThe two homologous chaperonin 60 proteins of<i>Mycobacterium tuberculosis</i>have distinct effects on monocyte differentiation into osteoclasts
dc.typejournal-article
dc.typeJournal Article
dc.typeResearch Support, Non-U.S. Gov't
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000259086900015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue10
plymouth.volume10
plymouth.publication-statusPublished
plymouth.journalCellular Microbiology
dc.identifier.doi10.1111/j.1462-5822.2008.01193.x
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/School of Biomedical Sciences
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
plymouth.organisational-group/Plymouth/Research Groups/Plymouth Institute of Health and Care Research (PIHR)
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dc.publisher.placeIndia
dc.identifier.eissn1462-5822
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1111/j.1462-5822.2008.01193.x
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review


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