SnoRNA signatures in cartilage ageing and osteoarthritis

Abstract

ObjectivesOsteoarthritis (OA) presents as a change in the chondrocyte phenotype and an imbalance between anabolic and catabolic processes. Age affects its onset and progression. Small nucleolar RNAs (SnoRNAs) direct chemical modification of RNA substrates to fine-tune spliceosomal and rRNA function, accommodating changing requirements for splicing and protein synthesis during health and disease. This study was undertaken to examine how changes in snoRNAs expression may have a role in OA. MethodsArticular cartilage from young, old and OA knees was used in a microarray study to identify alterations in snoRNA expression. Changes in expression of snoRNAs in OA-like conditions were studied in chondrocytes using interleukin-1 and OA synovial fluid. SNORD26 and SNORD96A knockdown and overexpression were undertaken using antisense oligonucleotides and overexpression plasmids. ResultsWe identified panels of snoRNAs differentially expressed due to ageing (including SNORD96A, SNORD44) and OA (including SNORD26 and SNORD116) and findings were validated in an independent cohort. In vitro experiments using OA-like conditions affected snoRNA expression. Knockdown or overexpression of SNORD26 or SNORD96A resulted in changes in chondrogenic, hypertrophic, rRNA and osteoarthritis related gene expression. ConclusionWe demonstrate that snoRNA expression changes in cartilage ageing, and OA and in OA-like conditions, and when the expression of these snoRNAs is altered this affects chondrogenic and hypertrophic gene expression. Thus, we propose an additional dimension in the molecular mechanisms underlying cartilage ageing and OA through the dysregulation of snoRNAs.