Swingler TE, Niu L, Smith P, Paddy P, Le L, Barter MJ et al. The function of microRNAs in cartilage and osteoarthritis. Clin Exp Rheumatol. 2019;37 Suppl 120:40 – 7.
Woods S, Charlton S, Cheung K, Hao Y, Soul J, Reynard LN, et al. microRNA-seq of cartilage reveals an overabundance of mir-140-3p which contains functional isomiRs. RNA. 2020;26:1575–88.
Mokuda S, Nakamichi R, Matsuzaki T, Ito Y, Sato T, Miyata K, et al. Wwp2 maintains cartilage homeostasis through regulation of Adamts5. Nat Commun. 2019;10:2429.
Miyaki S, Sato T, Inoue A, Otsuki S, Iko Y, Yokoyama S, et al. MicroRNA-140 plays dual roles in both cartilage development and homeostasis. Genes Dev. 2010;11:1173–85.
Nakamura Y, Inloes JB, Katagiri T, Kobayashi T. Chondrocyte-specific microRNA-140 regulates endochondral bone development and targets Dnpep to modulate bone morphogenic protein signaling. Mol Cell Biol. 2011;14:3019–28.
Inui M, Mokuda S, Sato T, Tamano M, Takada S, Asahara H. Dissecting the roles of miR-140 and its host gene. Nat Cell Biol. 2018;5:516–8.
van der Kraan PM. The changing role of TGFβ in healthy, ageing and osteoarthritic joints. Nat Rev Rheumatol. 2017;13:155–63.
Cherifi C, Monteagudo S, Lories RJ. Promising targets for therapy of osteoarthritis: a review on the wnt and TGF-β signaling pathways. Ther Adv Musculoskelet Dis. 2021;13:1759720X211006959.
Chantry A. WWP2 ubiquitin ligase and its isoforms: new biological insight and promising disease targets. Cell Cycle. 2011;10:2437–9.
Soond SM, Chantry A. How ubiquitination regulates the TGF-β signalling pathway: new insights and new players. BioEssays. 2011;33:749–58.
Chen W, Jiang X, Luo Z. WWP2: a multifunctional ubiquitin ligase gene. Pathol Oncol Res. 2014;20:799–803.
Scheffner M, Kumar S. Mammalian HECT ubiquitin-protein ligases: biological and pathophysiological aspects. Biochim Biophys Acta. 2014;1843:61–74.
Soond SM, Chantry A. Selective targeting of activating and inhibitory smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFβ signalling and EMT. Oncogene. 2011;30:2451–62.
Wahl LC, Watt JE, Yim HTT, De Bourcier D, Tolchard J, Soond SM, et al. Smad7 binds differentially to individual and tandem WW3 and WW4 domains of WWP2 ubiquitin ligase isoforms. Int J Mol Sci. 2019;20:4682.
Chen H, Moreno-Moral A, Pesce F, Devapragash N, Mancini M, Heng EL, et al. WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling. Nat Commun. 2019;10:3616.
Styrkarsdottir U, Lund SH, Thorleifsson G, Zink F, Stefansson OA, Sigurdsson JK, et al. Meta-analysis of Icelandic and UK data sets identifies missense variants in SMO, IL11, COL11A1 and 13 more new loci associated with osteoarthritis. Nat Genet. 2018;50:1681–7.
Tachmazidou I, Hatzikotoulas K, Southam L, Esparza-Gordillo J, Haberland V, Zheng J, et al. Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nat Genet. 2019;51:230–6.
Boer CG, Hatzikotoulas K, Southam L, Stefánsdóttir L, Zhang Y, Coutinho de Almeida R, et al. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell. 2021;184:4784–818.
Gallagher MD, Chen-Plotkin AS. The post-GWAS era: from association to function. Am J Hum Genet. 2018;102:717–30.
Boix CA, James BT, Park YP, Meuleman W, Kellis M. Regulatory genomic circuitry of human disease loci by integrative epigenomics. Nature. 2021;590:300–7.
Smith E, Shilatifard A. Enhancer biology and enhanceropathies. Nat Struct Mol Biol. 2014;21:210–9.
den Hollander W, Pulyakhina I, Boer C, Bomer N, van der Breggen R, Arindrarto W, et al. Annotating transcriptional effects of genetic variants in disease-relevant tissue: transcriptome-wide allelic imbalance in osteoarthritic cartilage. Arthritis Rheumatol. 2019;71:561–70.
23, Rice SJ, Cheung K, Reynard LN, Loughlin J. Discovery and analysis of methylation quantitative trait loci (mQTLs) mapping to novel osteoarthritis genetic risk signals. Osteoarthritis Cartilage. 2019;27:1545–56.
Aubourg G, Rice SJ, Bruce-Wootton P, Loughlin J. Genetics of osteoarthritis. Osteoarthritis Cartilage. 2022;30:636–49.
den Hollander W, Ramos YFM, Bomer N, Elzinga S, van der Breggen R, Lakenberg N, et al. Transcriptional associations of osteoarthritis-mediated loss of epigenetic control in articular cartilage. Arthritis Rheumatol. 2015;8:2108–16.
Hannon E, Gorrie-Stone TJ, Smart MC, Burrage J, Hughes A, Bao Y, et al. Leveraging DNA-methylation quantitative-trait loci to characterize the relationship between methylomic variation, gene expression, and complex traits. Am J Hum Genet. 2018;103:654–65.
Pierce BL, Tong L, Argos M, Demanelis K, Jasmine F, Rakibuz-Zaman M, et al. Co-occurring expression and methylation QTLs allow detection of common causal variants and shared biological mechanisms. Nat Commun. 2018;9:804.
Héberlé E, Bardet AF. Sensitivity of transcription factors to DNA methylation. Essays Biochem. 2019;63:727–41.
Parker E, Hofer IM, Rice SJ, Earl L, Anjum S, Deehan D, et al. Multi-tissue epigenetic and gene expression analysis combined with epigenome modulation identifies RWDD2B as a target of osteoarthritis susceptibility. Arthritis Rheumatol. 2021;73:100–9.
Rice SJ, Roberts JB, Tselepi M, Brumwell A, Falk J, Steven C, et al. Genetic and epigenetic fine-tuning of TGFB1 expression within the human osteoarthritic joint. Arthritis Rheumatol. 2021;73:1866–77.
Kehayova YS, Watson E, Wilkinson JM, Loughlin J, Rice SJ. Genetic and epigenetic interplay within a COLGALT2 enhancer associated with osteoarthritis. Arthritis Rheumatol. 2021;73:1856–65.
Brumwell A, Aubourg G, Hussain J, Parker E, Deehan DJ, Rice SJ, et al. Identification of TMEM129, encoding a ubiquitin-protein ligase, as an effector gene of osteoarthritis genetic risk. Arthritis Res Ther. 2022;24:189.
Rice SJ, Brumwell A, Falk J, Kehayova YS, Casement J, Parker E, et al. Genetic risk of osteoarthritis operates during human skeletogenesis. Hum Mol Genet. 2023;32:2124–38.
Kehayova YS, Wilkinson JM, Rice SJ, Loughlin J. Mediation of the same epigenetic and transcriptional effect by independent osteoarthritis risk-conferring alleles on a shared target gene, COLGALT2. Arthritis Rheumatol. 2023;75:910–22.
Lee BT, Barber GP, Benet-Pagès A, Casper J, Clawson H, Diekhans M, et al. The UCSC genome browser database: 2022 update. Nucleic Acids Res. 2022;50:D1115–22.
Roadmap Epigenomics Consortium. Integrative analysis of 111 reference human epigenomes. Nature. 2015;518:317–30.
Wang Y, Song F, Zhang B, Zhang L, Xu J, Kuang D, et al. The 3D genome browser: a web-based browser for visualizing 3D genome organization and long-range chromatin interactions. Genome Biol. 2018;19:151.
Castro-Mondragon JA, Riudavets-Puig R, Rauluseviciute I, Lemma RB, Turchi L, Blanc-Mathieu R, et al. JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 2022;50:D165–73.
Ajekigbe B, Cheung K, Xu Y, Skelton AJ, Panagiotopoulos A, Soul J, et al. Identification of long non-coding RNAs expressed in knee and hip osteoarthritic cartilage. Osteoarthritis Cartilage. 2019;27:694–702.
Kokenyesi R, Tan L, Robbins JR, Goldring MB. Proteoglycan production by immortalized human chondrocyte cell lines cultured under conditions that promote expression of the differentiated phenotype. Arch Biochem Biophys. 2000;383:79–90.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2– DDCT method. Methods. 2001;25:402–8.
Du P, Zhang X, Huang C-C, Jafari N, Kibbe WA, Hou L, et al. Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis. BMC Bioinformatics. 2010;11:587.
Richard D, Liu Z, Cao J, Kiapour AM, Willen J, Yarlagadda S, et al. Evolutionary selection and constraint on human knee chondrocyte regulation impacts osteoarthritis risk. Cell. 2020;181:362–81.
Richard D, Capellini TD. Shifting epigenetic contexts influence regulatory variation and disease risk. Aging. 2021;13:15699–749.
Kreitmaier P, Suderman M, Southam L, Coutinho de Almeida R, Hatzikotoulas K, Meulenbelt I, et al. An epigenome-wide view of osteoarthritis in primary tissues. Am J Hum Genet. 2022;109:1255–71.
Zhang F-J, Luo W, Lei G-H. Role of HIF-1a and HIF-2a in osteoarthritis. Joint Bone Spine. 2015;82:144–7.
Okada K, Mori D, Makii Y, Nakamoto H, Murahashi Y, Yano F, et al. Hypoxia-inducible factor-1 alpha maintains mouse articular cartilage through suppression of NF-kB signaling. Sci Rep. 2020;10:5425.
Tuerlings M, Janssen GMC, Boone I, van Hoolwerff M, Rodriguez Ruiz A, Houtman E, et al. WWP2 confers risk to osteoarthritis by affecting cartilage matrix deposition via hypoxia associated genes. Osteoarthritis Cartilage. 2023;31:39–48.
Watt JE, Hughes GR, Walpole S, Monaco S, Stephenson GR, Bulman Page PC, et al. Discovery of small molecule WWP2 ubiquitin ligase inhibitors. Chemistry. 2018;24:17677–80.
Add Comment