| http://purl.uniprot.org/citations/17950682 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17950682 | http://www.w3.org/2000/01/rdf-schema#comment | "BAG-1, an anti-apoptotic protein, was identified by its ability to bind to BCL-2, HSP70-family molecular chaperones and nuclear hormone receptor family members. Two BAG-1 isoforms, BAG-1L (50 kDa) and BAG-1S (32 kDa) were identified in mouse cells and BAG-1 expression was reported in murine growth plate and articular chondrocytes. The present study aimed to elucidate the role of BAG-1 in the regulation of molecular mechanisms governing chondrocyte differentiation and turnover during endochondral ossification. In long bones of skeletally immature mice, we observed expression of BAG-1 in the perichondrium, osteoblasts, osteocytes in the bone shaft, bone marrow, growth plate and articular chondrocytes. Monolayer cultures of murine chondrocytic ATDC5 cells, which exhibited robust expression of both BAG-1 isoforms and the Bag-1 transcript, were utilized as an in vitro model to delineate the roles of BAG-1. Overexpression of BAG-1L in ATDC5 cells resulted in downregulation of Col2a1 expression, a gene characteristically downregulated at the onset of hypertrophy, and an increase in transcription of Runx-2 and Alkaline phosphatase, genes normally expressed at the onset of chondrocyte hypertrophy and cartilage mineralization in the process of endochondral ossification. We also demonstrated the anti-apoptotic role of BAG-1 in chondrocytes as overexpression of BAG-1 protected ATDC5 cells, which were subjected to heat-shock at 48 degrees C for 30 min, against heat-shock-induced apoptosis. Overexpression of the SOX-9 protein in ATDC5 cells resulted in increased Bag-1 gene expression. To further investigate the regulation of Bag-1 gene expression by SOX-9, CHO cells were co-transfected with the human Bag-1 gene promoter-Luciferase reporter construct and the human pSox-9 expression vector. Activity of the Bag-1 promoter was significantly enhanced by the SOX-9 protein. In conclusion, a novel finding of this study is the role of BAG-1 as a transcriptional regulator of genes involved in chondrocyte hypertrophy and cartilage mineralization during the process of endochondral ossification. Additionally, we have demonstrated for the first time the regulation of Bag-1 gene expression by SOX-9 and the anti-apoptotic role of BAG-1 in chondrocytic cells. Modulation of Bag-1 expression can therefore mediate chondrocyte differentiation and turnover, and offer further insight into the molecular regulation of endochondral ossification."xsd:string |
| http://purl.uniprot.org/citations/17950682 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.bone.2007.08.032"xsd:string |
| http://purl.uniprot.org/citations/17950682 | http://purl.uniprot.org/core/author | "Oreffo R.O."xsd:string |
| http://purl.uniprot.org/citations/17950682 | http://purl.uniprot.org/core/author | "Inglis S."xsd:string |
| http://purl.uniprot.org/citations/17950682 | http://purl.uniprot.org/core/author | "Townsend P.A."xsd:string |
| http://purl.uniprot.org/citations/17950682 | http://purl.uniprot.org/core/author | "Tare R.S."xsd:string |
| http://purl.uniprot.org/citations/17950682 | http://purl.uniprot.org/core/author | "Packham G.K."xsd:string |
| http://purl.uniprot.org/citations/17950682 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/17950682 | http://purl.uniprot.org/core/name | "Bone"xsd:string |
| http://purl.uniprot.org/citations/17950682 | http://purl.uniprot.org/core/pages | "113-128"xsd:string |
| http://purl.uniprot.org/citations/17950682 | http://purl.uniprot.org/core/title | "Bcl-2-associated athanogene-1 (BAG-1): a transcriptional regulator mediating chondrocyte survival and differentiation during endochondral ossification."xsd:string |
| http://purl.uniprot.org/citations/17950682 | http://purl.uniprot.org/core/volume | "42"xsd:string |
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