Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/25707934http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25707934http://www.w3.org/2000/01/rdf-schema#comment"

Objective

In growth plate chondrocytes, loss of Dicer, a microRNA (miRNA)-processing enzyme, causes defects in proliferation and differentiation, leading to a lethal skeletal dysplasia. However roles of miRNAs in articular chondrocytes have not been defined in vivo. To investigate the role of miRNAs in articular chondrocytes and to explore the possibility of generating a novel mouse osteoarthritis (OA) model caused by intrinsic cellular dysfunction, we ablated Drosha, another essential enzyme for miRNA biogenesis, exclusively in articular chondrocytes of postnatal mice.

Design

First, to confirm that the essential role of miRNAs in skeletal development, we ablated the miRNA biogenesis pathway by deleting Drosha or DGCR8 in growth plate chondrocytes. Next, to investigate the role of miRNAs in articular cartilage, we deleted Drosha using Prg4-CreER(T) transgenic mice expressing a tamoxifen-activated Cre recombinase (CreER(T)) exclusively in articular chondrocytes. Tamoxifen was injected at postnatal days, 7, 14, 21, and 28 to ablate Drosha.

Results

Deletion of Drosha or DGCR8 in growth plate chondrocytes caused a lethal skeletal defect similar to that of Dicer deletion, confirming the essential role of miRNAs in normal skeletogenesis. Early postnatal Drosha deletion in articular chondrocytes significantly increased cell death and decreased Safranin-O staining. Mild OA-like changes, including surface erosion and cleft formation, were found in male mice at 6 months of age; however such changes in females were not observed even at 9 months of age.

Conclusions

Early postnatal Drosha deficiency induces articular chondrocyte death and can cause a mild OA-like pathology."xsd:string
http://purl.uniprot.org/citations/25707934http://purl.org/dc/terms/identifier"doi:10.1016/j.joca.2015.02.015"xsd:string
http://purl.uniprot.org/citations/25707934http://purl.uniprot.org/core/author"Kobayashi T."xsd:string
http://purl.uniprot.org/citations/25707934http://purl.uniprot.org/core/author"Zhang M."xsd:string
http://purl.uniprot.org/citations/25707934http://purl.uniprot.org/core/author"Blelloch R."xsd:string
http://purl.uniprot.org/citations/25707934http://purl.uniprot.org/core/author"Papaioannou G."xsd:string
http://purl.uniprot.org/citations/25707934http://purl.uniprot.org/core/author"Kozhemyakina E."xsd:string
http://purl.uniprot.org/citations/25707934http://purl.uniprot.org/core/author"Mirzamohammadi F."xsd:string
http://purl.uniprot.org/citations/25707934http://purl.uniprot.org/core/author"Chong M.W."xsd:string
http://purl.uniprot.org/citations/25707934http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25707934http://purl.uniprot.org/core/name"Osteoarthritis Cartilage"xsd:string
http://purl.uniprot.org/citations/25707934http://purl.uniprot.org/core/pages"1214-1220"xsd:string
http://purl.uniprot.org/citations/25707934http://purl.uniprot.org/core/title"Early postnatal ablation of the microRNA-processing enzyme, Drosha, causes chondrocyte death and impairs the structural integrity of the articular cartilage."xsd:string
http://purl.uniprot.org/citations/25707934http://purl.uniprot.org/core/volume"23"xsd:string
http://purl.uniprot.org/citations/25707934http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25707934
http://purl.uniprot.org/citations/25707934http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25707934
http://purl.uniprot.org/uniprot/#_E0CY90-mappedCitation-25707934http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25707934
http://purl.uniprot.org/uniprot/#_E0CZ58-mappedCitation-25707934http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25707934
http://purl.uniprot.org/uniprot/#_A0A0R4J207-mappedCitation-25707934http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25707934
http://purl.uniprot.org/uniprot/#_A0A338P666-mappedCitation-25707934http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25707934
http://purl.uniprot.org/uniprot/#_A1L3C5-mappedCitation-25707934http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25707934
http://purl.uniprot.org/uniprot/#_E0CXA1-mappedCitation-25707934http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25707934
http://purl.uniprot.org/uniprot/#_E9QQ17-mappedCitation-25707934http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25707934
http://purl.uniprot.org/uniprot/#_E9QQ18-mappedCitation-25707934http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25707934
▶