{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:27:10Z","timestamp":1790497630529,"version":"4.1.0"},"reference-count":89,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>An imbalance in gene expressional events skewing chondrocyte anabolic and catabolic pathways toward the latter causes an aberrant turnover and loss of extracellular matrix proteins in osteoarthritic (OA) articular cartilage. Thus, catabolism results in the elevated loss of extracellular matrix proteins. There is also evidence of an increase in the frequency of chondrocyte apoptosis that compromises the capacity of articular cartilage to undergo repair. Although much of the fundamental OA studies over the past 20 years identified and characterized many genes relevant to pro-inflammatory cytokines, apoptosis, and matrix metalloproteinases (MMPs)\/a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS), more recent studies focused on epigenetic mechanisms and the associated role of microRNAs (miRs) in regulating gene expression in OA cartilage. Thus, several miRs were identified as regulators of chondrocyte signaling pathways, apoptosis, and proteinase gene expression. For example, the reduced expression of miR-146a was found to be coupled to reduced type II collagen (COL2) in OA cartilage, whereas MMP-13 levels were increased, suggesting an association between MMP-13 gene expression and COL2A1 gene expression. Results of these studies imply that microRNAs could become useful in the search for diagnostic biomarkers, as well as providing novel therapeutic targets for intervention in OA.<\/jats:p>","DOI":"10.3390\/cells7080092","type":"journal-article","created":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T11:22:34Z","timestamp":1533122554000},"page":"92","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["MicroRNAs and Osteoarthritis"],"prefix":"10.3390","volume":"7","author":[{"given":"Charles J.","family":"Malemud","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Rheumatic Diseases, University Hospitals Cleveland Medical Center, Foley Medical Building, 2061 Cornell Road, Cleveland, OH 44106-5076, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"367","DOI":"10.2174\/138945007779940061","article-title":"In vivo osteoarthritis target validation utilizing genetically-modified mice","volume":"8","author":"Glasson","year":"2007","journal-title":"Curr. Drug Targets"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.jcyt.2016.02.001","article-title":"Novel therapeutic targets in osteoarthritis: Narrative review on knock-out genes involved in disease development in mouse animal models","volume":"18","author":"Veronesi","year":"2016","journal-title":"Cytotherapy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.arr.2017.07.004","article-title":"Aging and osteoarthritis: Central role of the extracellular matrix","volume":"40","author":"Rahmati","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/BOR.0000000000000162","article-title":"Biological basis of osteoarthritis: State of the evidence","volume":"27","author":"Malemud","year":"2015","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.maturitas.2014.12.003","article-title":"Chondrosenescence: Definition, hallmarks and potential role in the pathogenesis of osteoarthritis","volume":"80","author":"Mobasheri","year":"2015","journal-title":"Maturitas"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e222","DOI":"10.1111\/sms.12290","article-title":"Physical activity ameliorates cartilage degeneration in a rat model of aging: A study on lubricin expression","volume":"25","author":"Musumeci","year":"2015","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.2174\/13816128113196660701","article-title":"Metalloproteinases and metalloproteinase inhibitors in age-related diseases","volume":"20","author":"Gargiulo","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_8","unstructured":"Malemud, C.J. (2013). Role of Proteases in Cellular Dysfunction, Springer Science."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nrrheum.2010.196","article-title":"Role of proinflammatory cytokines in the pathophysiology of osteoarthritis","volume":"7","author":"Kapor","year":"2011","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1749-6632.2011.06258.x","article-title":"Recent progress in understanding molecular mechanisms of cartilage degeneration during osteoarthritis","volume":"1240","author":"Wang","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/2040622312454157","article-title":"Prospects for treating osteoarthritis: Enzyme-protein interactions regulating matrix metalloproteinase activity","volume":"3","author":"Meszaros","year":"2012","journal-title":"Adv. Ther. Chronic Dis."},{"key":"ref_12","first-page":"e101","article-title":"The medical therapy of osteoarthritis: \u201cThinking outside the box\u201d","volume":"1","author":"Malemud","year":"2016","journal-title":"J. Osteoarthr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.3899\/jrheum.100759","article-title":"Pain mechanisms in osteoarthritis: Understanding the role of central pain and current approaches to its treatment","volume":"38","author":"Mease","year":"2011","journal-title":"J. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.berh.2015.04.017","article-title":"Osteoarthritis pain","volume":"29","author":"Perrot","year":"2015","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"iv99","DOI":"10.1093\/rheumatology\/kex522","article-title":"What is new in pain modification in osteoarthritis?","volume":"57","author":"Miller","year":"2018","journal-title":"Rheumatol. (Oxf. UK)"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"253","DOI":"10.2217\/17460816.3.3.253","article-title":"Is there a final common pathway for arthritis?","volume":"3","author":"Schulte","year":"2008","journal-title":"Future Rheumatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2174\/1573397054023146","article-title":"The role of apoptosis in arthritis","volume":"1","author":"Malemud","year":"2005","journal-title":"Curr. Rheum. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Charlier, E., Relic, B., Deroyer, C., Malaise, O., Neuville, S., Coll\u00e9e, J., Malaise, M.G., and De Seny, D. (2016). Insights on molecular mechanisms of chondrocyte death in osteoarthritis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122146"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"20560","DOI":"10.3390\/ijms160920560","article-title":"Biomarkers of chondrocyte apoptosis and autophagy in osteoarthritis","volume":"16","author":"Musumeci","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_20","first-page":"1265","article-title":"OA cartilage derived chondrocytes encapsulated in poly (ethylene glycol) diacrylate (PEGDA) for the evaluation of cartilage restoration and apoptosis in an in vitro model","volume":"26","author":"Musumeci","year":"2011","journal-title":"Histol. Histopathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s00167-010-1215-0","article-title":"Characterization of apoptosis in articular cartilage derived from knee joints of patients with osteoarthritis","volume":"19","author":"Musumeci","year":"2011","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3293","DOI":"10.2174\/1381612811209023293","article-title":"Insights on biology and pathology of HIF-1\u03b1\/2\u03b1, TGF\u00df\/BMP, Wnt\/\u00df-catenin, and NF-\u03baB pathways in osteoarthritis","volume":"18","author":"Wu","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e460","DOI":"10.3928\/01477447-20140430-57","article-title":"Tissue levels of leukemia inhibitory factor vary by osteoarthritis grade","volume":"37","author":"Jiang","year":"2014","journal-title":"Orthopedics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"R126","DOI":"10.1186\/ar4306","article-title":"GREM1, FRZB, and DKK1 mRNA levels correlate with osteoarthritis and are regulated by osteoarthritis-related factors","volume":"15","author":"Leitjen","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.joca.2014.01.001","article-title":"Modeling of signaling pathways in osteoarthritis based on phosphoproteomics and cytokine release data","volume":"22","author":"Melas","year":"2014","journal-title":"Osteoarthr. Cartil."},{"key":"ref_26","first-page":"193","article-title":"Clinical significance and implications of genetic and genomic studies in patients with osteoarthritis","volume":"4","author":"Muoh","year":"2014","journal-title":"Adv. Genom. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s13075-017-1296-y","article-title":"Molecular mechanisms underlying osteoarthritis development: Notch and NF-\u03baB","volume":"19","author":"Saito","year":"2017","journal-title":"Arthritis Res. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/jcb.10317","article-title":"Hydrostatic pressure induces apoptosis in human chondrocytes from osteoarthritic cartilage through up-regulation of tumor necrosis factor-\u03b1, inducible nitric oxide synthase, p53, c-myc and bax-\u03b1 and suppression of bcl-2","volume":"87","author":"Islam","year":"2002","journal-title":"J. Cell Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S145","DOI":"10.1097\/01.blo.0000143802.41885.50","article-title":"Protein kinases in chondrocyte signaling and osteoarthritis","volume":"427","author":"Malemud","year":"2004","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/ar1197","article-title":"Signaling by STATs","volume":"6","author":"Ivashkiv","year":"2004","journal-title":"Arthritis Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.immuni.2012.03.013","article-title":"The JAK-STAT pathway at 20","volume":"36","author":"Stark","year":"2012","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Malemud, C.J. (2017). Negative regulators of JAK\/STAT signaling in rheumatoid arthritis and osteoarthritis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18030484"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Akeson, G., and Malemud, C.J. (2017). A role for soluble IL-6 receptor in osteoarthritis. J. Funct. Morphol. Kinesiol., 2.","DOI":"10.3390\/jfmk2030027"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3389\/fbioe.2018.00022","article-title":"Interplay of inflammatory mediators with epigenetics and cartilage modifications in osteoarthritis","volume":"6","author":"Raman","year":"2018","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fbioe.2018.00018","article-title":"Recent insights into the contribution of the changing hypertrophic chondrocyte phenotype in the development and progression of osteoarthritis","volume":"6","author":"Ripmeester","year":"2018","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1097\/BOR.0000000000000471","article-title":"Epigenetics of inflammatory arthritis","volume":"30","author":"Hammaker","year":"2018","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.gendis.2014.12.005","article-title":"Epigenetics and osteoarthritis","volume":"2","author":"Zhang","year":"2015","journal-title":"Genes Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3390\/jfmk1010140","article-title":"The genetics of osteoarthritis: A. review","volume":"1","author":"Warner","year":"2016","journal-title":"J. Funct. Morphol. Kinesiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3720128","DOI":"10.1155\/2017\/3720128","article-title":"MicroRNAs and autophagy: Fine players in the control of chondrocyte homeostatic activities in osteoarthritis","volume":"2017","author":"Cetrullo","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/147323001103900101","article-title":"MicroRNA in osteoarthritis","volume":"39","author":"Yu","year":"2011","journal-title":"J. Int. Med. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nrrheum.2012.128","article-title":"Macro view of microRNA function in osteoarthritis","volume":"8","author":"Miyaki","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1007\/s11926-016-0604-x","article-title":"The role of microRNAs and their targets in osteoarthritis","volume":"18","author":"Sondag","year":"2016","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_43","first-page":"518","article-title":"Do microRNAs have a key epigenetic role in osteoarthritis and in mechanotransduction?","volume":"35","author":"Cheleschi","year":"2017","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"239","DOI":"10.4172\/2167-7921.1000239","article-title":"Role of microRNA in osteoarthritis","volume":"6","author":"Zhang","year":"2017","journal-title":"J. Arthritis"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1007\/s11914-014-0229-9","article-title":"MicroRNAs in cartilage development, homeostasis and disease","volume":"12","author":"Mirzamohammad","year":"2014","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3892\/ijmm.2014.1743","article-title":"MicroRNAs play a role in chondrogenesis and osteoarthritis (review)","volume":"34","author":"Wu","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"393","DOI":"10.2174\/1389202916666150817203144","article-title":"The role of microRNAs in cartilage homeostasis","volume":"16","author":"Li","year":"2015","journal-title":"Curr. Genom."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jbspin.2015.06.009","article-title":"Autophagy in osteoarthritis","volume":"83","author":"Li","year":"2016","journal-title":"Jt. Bone Spine"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.joca.2015.10.018","article-title":"MicroRNAs: Exploring new horizons in osteoarthritis","volume":"24","author":"Nugent","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1016\/j.joca.2017.03.012","article-title":"A bioinformatics analysis of microRNAs role in osteoarthritis","volume":"25","author":"Cong","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_51","first-page":"2177","article-title":"miR-138 suppressed the progression of osteoarthritis mainly through targeting p65","volume":"21","author":"Wei","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"12775","DOI":"10.1038\/srep12775","article-title":"MiR-210 inhibits NF-\u03baB signaling pathway by targeting DR6 in osteoarthritis","volume":"5","author":"Zhang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"551","DOI":"10.3892\/mmr.2016.6035","article-title":"Reduced miR-26a and miR-26b expression contributes to the pathogenesis of osteoarthritis via the promotion of p65 translocation","volume":"15","author":"Yin","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.bbrc.2016.03.164","article-title":"miR-139 is up-regulated in osteoarthritis and inhibits chondrocyte proliferation and migration possibly via suppressing EIF4G2 and IGF1R","volume":"474","author":"Hu","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.amjms.2018.01.004","article-title":"MicroRNA-140 suppresses human chondrocyte hypertrophy by targeting SMAD1 and controlling bone morphogenetic protein pathway in osteoarthritis","volume":"355","author":"Li","year":"2018","journal-title":"Am. J. Med. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"103","DOI":"10.14348\/molcells.2016.2179","article-title":"MiR-29 and MiR-140 protect chondrocytes against the anti-proliferation and cell matrix signaling changes by IL-1\u00df","volume":"39","author":"Li","year":"2016","journal-title":"Mol. Cells"},{"key":"ref_57","first-page":"2555","article-title":"Decreased expression of microRNA-130a correlates with TNF-\u03b1 in the development of osteoarthritis","volume":"8","author":"Li","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Li, X., He, P., Li, Z., Wang, H., Liu, M., Xiao, Y., Xu, D., Kang, Y., and Wang, H. (2018). Interleukin-1\u00df-mediated suppression of microRNA-27a-3p activity in human cartilage via MAPK and NF-\u03baB pathways: A potential mechanism of osteoarthritis pathogenesis. Mol. Med. Rep.","DOI":"10.3892\/mmr.2018.8970"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.bbrc.2016.06.071","article-title":"MicroRNA-23a-3p promotes the development of osteoarthritis by directly targeting SMAD3 in chondrocytes","volume":"478","author":"Kang","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"23117","DOI":"10.1038\/srep23117","article-title":"Overexpression of microRNA-634 suppresses survival and matrix synthesis of human osteoarthritis chondrocytes by targeting PIK3R1","volume":"6","author":"Cui","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1016\/j.joca.2016.07.002","article-title":"Inhibition of microRNA-449a prevent IL-1\u00df-induced cartilage destruction via SIRT1","volume":"24","author":"Park","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1002\/art.39173","article-title":"MicroRNA-9 promotion of interleukin-6 expression by inhibiting monocyte chemoattractant protein-induced protein 1 expression in interleukin-1\u00df-stimulated human chondrocytes","volume":"67","author":"Makki","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s00109-015-1374-z","article-title":"The microRNA-29 family in cartilage homeostasis and osteoarthritis","volume":"94","author":"Le","year":"2016","journal-title":"J. Mol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.joca.2016.11.006","article-title":"MicroRNA-92a-3p regulates the expression of cartilage-specific genes by directly targeting histone deacetylase 2 in chondrogenesis and degradation","volume":"25","author":"Mao","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Chen, W., Sheng, P., Huang, Z., Meng, F., Kang, Y., Huang, G., Zhang, Z., Liao, W., and Zhang, Z. (2016). MicroRNA-381 regulates chondrocyte hypertrophy by inhibiting histone deacetylase 4 expression. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091377"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1111\/acel.12363","article-title":"miR-370 and miR-373 regulate the pathogenesis of osteoarthritis by modulating one-carbon metabolism via SHMT-2 and MECP-2, respectively","volume":"14","author":"Song","year":"2015","journal-title":"Aging Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e79","DOI":"10.1038\/emm.2013.152","article-title":"MicroRNA-21 controls the development of osteoarthritis by targeting GDF5 in chondrocytes","volume":"46","author":"Zhang","year":"2014","journal-title":"Exp. Mol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"9792512","DOI":"10.1155\/2017\/9792512","article-title":"MicroRNA-29b contributes to collagen imbalance in human osteoarthritic and dedifferentiated articular chondrocytes","volume":"2017","author":"Moulin","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e2734","DOI":"10.1038\/cddis.2017.146","article-title":"miR-146a facilitates osteoarthritis by regulating cartilage homeostasis via targeting Camk2d and Ppp3r2","volume":"8","author":"Zhang","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"46704","DOI":"10.1038\/srep46704","article-title":"MiR-146b is down-regulated during the chondrogenic differentiation of human bone marrow derived skeletal stem cells and up-regulated in osteoarthritis","volume":"7","author":"Budd","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1016\/j.joca.2016.01.005","article-title":"MicroRNA-155 suppresses autophagy in chondrocytes by modulating expression of autophagy proteins","volume":"24","author":"Muramastu","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1159\/000453147","article-title":"AntimiR-30b inhibits TNF-\u03b1 mediated apoptosis and attenuated cartilage degradation through enhancing autophagy","volume":"40","author":"Chen","year":"2016","journal-title":"Cell Physiol. Biochem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3958","DOI":"10.3892\/mmr.2017.7064","article-title":"Beclin overexpression inhibits chondrocyte apoptosis and downregulates extracellular matrix metabolism in osteoarthritis","volume":"16","author":"Song","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/art.24404","article-title":"Expression of MicroRNA-146a in osteoarthritic cartilage","volume":"60","author":"Yamasaki","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"451","DOI":"10.3892\/ijmm.2014.1808","article-title":"Role of miR-146a in human chondrocyte apoptosis in response to mechanical pressure injury in vitro","volume":"34","author":"Jin","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3892\/ijmm.2016.2618","article-title":"MicroRNA-34a affects chondrocyte apoptosis and proliferation by targeting the SIRT1\/p53 signaling pathway during the pathogenesis of osteoarthritis","volume":"38","author":"Yan","year":"2016","journal-title":"Int. J. Mol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1139\/bcb-2016-0078","article-title":"MicroRNA-181 inhibits proliferation and promotes apoptosis of chondrocytes in osteoarthritis by targeting PTEN","volume":"95","author":"Wu","year":"2017","journal-title":"Biochem. Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.4155\/fmc.15.55","article-title":"PI3K\/Akt\/PTEN\/mTOR signaling: A fruitful target for inducing cell death in rheumatoid arthritis?","volume":"7","author":"Malemud","year":"2015","journal-title":"Future Med. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1002\/jor.22718","article-title":"A long non-coding RNA, GAS5, plays a crucial role in the regulation of miR-21 during osteoarthritis","volume":"32","author":"Song","year":"2014","journal-title":"J. Orthop. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.bbacli.2014.11.009","article-title":"MicroRNA-222 regulates MMP-13 via targeting HDAC-4 during osteoarthritis pathogenesis","volume":"3","author":"Song","year":"2014","journal-title":"BBA Clin."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"R58","DOI":"10.1186\/ar4494","article-title":"P161NK4a and its regulator miR-24 link senescence and chondrocyte terminal differentiation-associated matrix remodeling in osteoarthritis","volume":"16","author":"Philpot","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.joca.2015.12.012","article-title":"MicroRNA-320 regulates matrix metalloproteinase-13 expression in chondrogenesis and interleukin-1\u00df-induced chondrocyte responses","volume":"24","author":"Meng","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1302\/2046-3758.64.BJR-2016-0224.R1","article-title":"The role of miR-320a and IL-1\u00df in human chondrocyte degradation","volume":"6","author":"Jin","year":"2017","journal-title":"Bone Jt. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s00109-016-1380-9","article-title":"miR-105\/Runx2 axis mediates FGF2-induced ADAMTS5 expression in osteoarthritis","volume":"94","author":"Ji","year":"2016","journal-title":"J. Mol. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1159\/000484579","article-title":"MicroRNA-92a-3p regulates aggrecanase\u20141 and aggrecanase-2 expression in chondrogenesis and IL-1\u00df-induced catabolism in human articular chondrocytes","volume":"44","author":"Mao","year":"2017","journal-title":"Cell Physiol. Biochem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s00109-016-1418-z","article-title":"The IL-1\u00df\/AP-1\/miR-30a\/ADAMTS-5 axis regulates cartilage matrix degradation in human osteoarthritis","volume":"94","author":"Ji","year":"2016","journal-title":"J. Mol. Med. (Berl.)"},{"key":"ref_87","first-page":"2509","article-title":"Chondrocyte death in experimental osteoarthritis is mediated by MEK1\/2 and p38 pathways: Role of cyclooxygenase-2 and inducible nitric oxide synthase","volume":"28","author":"Pelletier","year":"2001","journal-title":"J. Rheumatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1159\/000070573","article-title":"Pathophysiological mechanisms in osteoarthritis lead to novel therapeutic strategies","volume":"174","author":"Malemud","year":"2003","journal-title":"Cells Tissues Organs"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1002\/art.40456","article-title":"Impaired proteasomal function in human osteoarthritic chondrocytes can contribute to decreased levels of SOX9 and aggrecan","volume":"70","author":"Serrano","year":"2018","journal-title":"Arthritis Rheumatol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/7\/8\/92\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:15:46Z","timestamp":1760195746000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/7\/8\/92"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,1]]},"references-count":89,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2018,8]]}},"alternative-id":["cells7080092"],"URL":"https:\/\/doi.org\/10.3390\/cells7080092","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,1]]}}}