The role of microRNA 144 in osteoarthritis

Abstract

versus OOA; SNORD74 and SNORD77. The latter was accompanied by an increase in GAS5 expression in OA. P53 signalling has been implicated in cartilage ageing and OA. The expression of SNHG1, which along with its intronic snoRNAs have previously been identified as being repressed by p53 activation was reduced in ageing and increased in OA in parallel with one of its intronic snoRNAs SNORD26. HAGR identified eight agerelated host genes, including RLP13A, RPS12 in Y versus ON contrast. Six host genes were identified as age-related in the ON1 versus ON2 contrast, including RPL13A and RPS12. The top canonical pathways identified from Y versus ON host genes were EIF2 (p¼1.7E-25), mTOR signalling (p¼2.1E-09) and regulation of EIF4 and p70S6K signalling (p¼7.1E-09) and for ON versus OOA were EIF2 signalling (p¼3.1E-12), regulation of EIF4 and p70S6K signalling (p¼3.6E-04) and mTOR signalling (p¼7.2E-04). The top networks identified in Y versus ON was 'cell death and survival and organismal injury', and for ON versus OOA was 'immunological disease'. Conclusions: Previously it was thought that as many host genes contained short, poorly conserved, open reading frames that they had no function other than carry the snoRNAs sequence within their introns. However work in cancer has identified that some host genes have roles in tumorigenesis and cell fate. Many of the protein coding snoRNA host genes are involved in protein synthesis enabling co-regulation of snoRNAs and proteins implicated in translation. mTOR signalling, is implicated in cartilage homeostasis and cartilage degeneration associated with OA. This was one of the principal pathways that host genes contributed to and host genes were within multiple levels of the signalling pathway. Our work points to additional, as yet undefined roles for some of these snoRNA host genes in cartilage ageing and OA, both through the production of the snoRNAs which they express, and through functions of the genes themselves. THEPurpose: Synovitis is a characteristic feature of both early and endstage OA. However, the cellular mechanisms that regulate synovial tissue inflammation are poorly understood. Importantly, we recently identified through Next Generation Sequencing (NGS) several long non coding RNAs (lncRNAs) that were associated with the IL-1b inflammatory response in OA chondrocytes, and which regulated the secretion of pro-inflammatory cytokines including IL-6. The purpose of the present study was firstly to identify lncRNAs expressed in fibroblast-like synoviocytes (FLS) that were associated with inflammatory OA synovial tissue. Secondly to examine their expression in OA synovium compared to non-OA synovial tissue, and thirdly to determine whether modulation of the expression of an inflammatory-associated lncRNA affected the phenotype of isolated OA FLS cells. Methods: Synovial tissue was collected from end-stage hip OA patients and from neck of femur fracture patients without OA (NOF#) undergoing total hip arthroplasty (NRES 14/ES/1044). Fibroblast-like synoviocytes (FLS) were...

LINC01534 Promotes the Aberrant Metabolic Dysfunction and Inflammation in IL-1β-Simulated Osteoarthritic Chondrocytes by Targeting miR-140-5p

“…In the present study, IL-1β induction was used to establish the OA chondrocyte model, and qRT-PCR results showed that LINC01534 was also highly expressed in the OA chondrocyte model. Studies have found that lncRNA can be used as a ceRNA to bind miRNA, thereby inhibiting the function of miRNA and affecting the pathogenesis of OA (25). MiR-140-5p is not only abnormally expressed in various tumor tissues, but also involved in the pathogenesis of rheumatoid arthritis and knee osteoarthritis (26)(27)(28)(29).…”

“…Studies have found that lncRNA can be used as a ceRNA to bind miRNA, thereby inhibiting the function of miRNA and affecting the pathogenesis of OA. 25 MiR-140-5p is not only abnormally expressed in various tumor tissues but also involved in the pathogenesis of rheumatoid arthritis and knee osteoarthritis. 26-29 However, the interaction mechanism between LINC01534 and miR-140-5p in the development of OA is still unclear.…”

ABCA1 is direct target gene of miR-144-3p in chondrocyte

“…A study examining the role of miR-144-3p in OA development in mice found that miR-144-3p was increased in the early stages of OA (Zhang et al, 2017). Our previous study also demonstrated that miR-144-3p is involved in the development of OA (Le et al, 2018). However, the role and function of the miRNA in OA pathogenesis remains unclear.…”

ABCA1 có thể đích tiềm năng của miRNA-144 trong tế bào sụn

“…Trong một nghiên cứu kiểm tra vai trò của miR-144-3p trong sự phát triển thoái hóa khớp ở chuột đã nhận thấy sự tăng biểu hiện của miR-144-3p ở giai đoạn đầu của thoái hóa khớp (Zhang, Lygrisse, & Wang, 2017). Tại Việt Nam, miR-144-3p được xác định có biểu hiện tăng trong thoái hoá khớp và đây là phân tử tiềm năng hỗ trợ trong chẩn đoán và điều trị nhiều bệnh ở người trong tương lai (Le, Ho, & Clark, 2018). Trước khi ứng dụng quy trình chẩn đoán và điều trị trong tương lai bằng cách sử dụng microRNA này, việc xác định chức năng của miR-144-3p là rất cần thiết.…”