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http://purl.uniprot.org/citations/36088855http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36088855http://www.w3.org/2000/01/rdf-schema#comment"Synovial tissue hyperplasia is a major cause of bone damage in rheumatoid arthritis (RA). Over-proliferation and secretion of cytokines of fibroblast-like synoviocytes (FLSs) are key contributors to bone damage in the joint microenvironment. Therefore, inhibition of FLSs-mediated bone damage is of great significance in RA patients. The aim of this study was to investigate the molecular mechanisms by which FLSs-mediated bone damage in the joint microenvironment. The results of whole transcriptome sequencing showed that Spp1 gene expression was significantly upregulated in collagen-induced arthritis FLSs compared to Normal FLSs. KEGG enrichment analysis revealed up-regulated Spp1 gene expression, associated with PI3K/AKT signaling. Animal and cellular experiments were designed to validate and explore the results of sequencing. Briefly, the data demonstrated secretory phosphoprotein 1 (SPP1) (encoded by Spp1 gene) secreted by FLSs promotes osteoclasts differentiation in vivo and in vitro and exacerbates articular bone damage in collagen-induced arthritis mice. Interestingly, SPP1 secreted by FLSs does not affect its own proliferation and apoptosis. The results of co-culture of FLSs with bone marrow-derived monocytes indicated the level of SPP1 secreted by FLSs positively correlates with the frequency of p-PI3K+PI3K+ osteoclasts, whereas not with the frequency of p-AKT+AKT+ osteoclasts. This may suggest that SPP1 secreted by FLSs acts directly on PI3K while indirectly on AKT. Together, the results revealed SPP1 secreted by FLSs promotes osteoclasts formation via PI3K/AKT signaling in collagen-induced arthritis. Regulation of Spp1 gene expression in FLSs may be a potential approach to treat RA bone damage in the joint microenvironment."xsd:string
http://purl.uniprot.org/citations/36088855http://purl.org/dc/terms/identifier"doi:10.1016/j.biopha.2022.113687"xsd:string
http://purl.uniprot.org/citations/36088855http://purl.uniprot.org/core/author"Cai X."xsd:string
http://purl.uniprot.org/citations/36088855http://purl.uniprot.org/core/author"Zheng Y."xsd:string
http://purl.uniprot.org/citations/36088855http://purl.uniprot.org/core/author"Zhang S."xsd:string
http://purl.uniprot.org/citations/36088855http://purl.uniprot.org/core/author"Ren F."xsd:string
http://purl.uniprot.org/citations/36088855http://purl.uniprot.org/core/author"Wu L."xsd:string
http://purl.uniprot.org/citations/36088855http://purl.uniprot.org/core/author"Yao Y."xsd:string
http://purl.uniprot.org/citations/36088855http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/36088855http://purl.uniprot.org/core/name"Biomed Pharmacother"xsd:string
http://purl.uniprot.org/citations/36088855http://purl.uniprot.org/core/pages"113687"xsd:string
http://purl.uniprot.org/citations/36088855http://purl.uniprot.org/core/title"Secretory phosphoprotein 1 secreted by fibroblast-like synoviocytes promotes osteoclasts formation via PI3K/AKT signaling in collagen-induced arthritis."xsd:string
http://purl.uniprot.org/citations/36088855http://purl.uniprot.org/core/volume"155"xsd:string
http://purl.uniprot.org/citations/36088855http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/36088855
http://purl.uniprot.org/citations/36088855http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/36088855
http://purl.uniprot.org/uniprot/#_D3Z116-mappedCitation-36088855http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36088855
http://purl.uniprot.org/uniprot/#_D3Z4N2-mappedCitation-36088855http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36088855
http://purl.uniprot.org/uniprot/#_D3Z513-mappedCitation-36088855http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36088855
http://purl.uniprot.org/uniprot/#_F8WIP8-mappedCitation-36088855http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36088855
http://purl.uniprot.org/uniprot/#_Q3UZY3-mappedCitation-36088855http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36088855
http://purl.uniprot.org/uniprot/#_P10923-mappedCitation-36088855http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36088855
http://purl.uniprot.org/uniprot/#_Q3TLP1-mappedCitation-36088855http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36088855
http://purl.uniprot.org/uniprot/#_Q3TND2-mappedCitation-36088855http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36088855
http://purl.uniprot.org/uniprot/#_Q66JX3-mappedCitation-36088855http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36088855