dc.creatorSabbagh, Yves
dc.creatorGraciolli, Fabiana Giorgeti
dc.creatorO'Brien, Stephen
dc.creatorTang, Wen
dc.creatordos Reis, Luciene Machado
dc.creatorRyan, Susan
dc.creatorPhillips, Lucy
dc.creatorBoulanger, Joseph
dc.creatorSong, Wenping
dc.creatorBracken, Christina
dc.creatorLiu, Shiguang
dc.creatorLedbetter, Steven
dc.creatorDechow, Paul
dc.creatorCanziani, Maria Eugenia F.
dc.creatorCarvalho, Aluizio B.
dc.creatorJorgetti, Vanda
dc.creatorMoyses, Rosa M. A.
dc.creatorSchiavi, Susan C.
dc.date.accessioned2013-11-05T11:46:04Z
dc.date.accessioned2018-07-04T16:13:51Z
dc.date.available2013-11-05T11:46:04Z
dc.date.available2018-07-04T16:13:51Z
dc.date.created2013-11-05T11:46:04Z
dc.date.issued2012
dc.identifierJOURNAL OF BONE AND MINERAL RESEARCH, HOBOKEN, v. 27, n. 8, supl. 1, Part 1, pp. 1757-1772, AUG, 2012
dc.identifier0884-0431
dc.identifierhttp://www.producao.usp.br/handle/BDPI/41258
dc.identifier10.1002/jbmr.1630
dc.identifierhttp://dx.doi.org/10.1002/jbmr.1630
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1633168
dc.description.abstractChronic kidney diseasemineral bone disorder (CKD-MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft-tissue calcification. Emerging evidence suggests that features of CKD-MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild-type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD-MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild-type mice. To capture the early molecular and cellular events in the progression of CKD-MBD we examined cell-specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor-Ser33/37-beta-catenin was observed both in mouse and human bones. Overall repression of Wnt/beta-catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF-?B ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late-stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD-MBD and suggest that repression of the Wnt/beta-catenin pathway is involved in the pathogenesis of renal osteodystrophy. (C) 2012 American Society for Bone and Mineral Research.
dc.languageeng
dc.publisherWILEY-BLACKWELL
dc.publisherHOBOKEN
dc.relationJOURNAL OF BONE AND MINERAL RESEARCH
dc.rightsCopyright WILEY-BLACKWELL
dc.rightsrestrictedAccess
dc.subjectRENAL OSTEODYSTROPHY
dc.subjectOSTEOCYTE
dc.subjectWNT
dc.subjectSS-CATENIN
dc.titleRepression of osteocyte Wnt/beta-catenin signaling is an early event in the progression of renal osteodystrophy
dc.typeArtículos de revistas


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