{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T13:16:38Z","timestamp":1775308598798,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T00:00:00Z","timestamp":1612656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2015R1D1A1A01060157"],"award-info":[{"award-number":["NRF-2015R1D1A1A01060157"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>High tibial osteotomy (HTO) is an effective alternative for medial compartmental knee osteoarthritis (OA). Circulating microRNAs (miRNAs) are known to serve as OA-related biomarkers. The present study investigated the differential expression of serum miRNAs before and after HTO to identify potential miRNAs as prognostic biomarkers. miRNA-polymerase chain reaction (PCR) arrays were used to screen for miRNAs in the serum at preoperative and 6-month postoperative time points from six patients, and the differentially expressed miRNAs identified in the profiling stage were validated using real-time PCR at post-operative months 6 and 18 in 27 other HTO-treated patients. Among 84 miRNAs involved in the inflammatory process, three (miR-19b-3p, miR-29c-3p, and miR-424-5p) showed differential expression patterns in the profiling stage (p = 0.011, 0.015, and 0.021, respectively). Levels of these three and four other miRNAs (miR-140-3p, miR-454-3p, miR-let-7e-5p, and miR-885-5p) known to be related to OA progression were evaluated in the serum of 27 patients. Only four miRNAs (miR-19b-3p, miR-140-3p, miR-454-3p, and miR-let-7e-5p) were significantly upregulated at postoperative month 6 (p = 0.003, 0.005, 0.004, and 0.004, respectively), and only miR-140-3p was significantly upregulated up to 18 months after operation (p = 0.003). Together, this study reveals the significantly upregulated serum miRNAs after HTO as potential prognostic biomarkers; however, further studies are warranted to elucidate their clinical implications.<\/jats:p>","DOI":"10.3390\/diagnostics11020258","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T20:51:51Z","timestamp":1612817511000},"page":"258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Significant Changes in Serum MicroRNAs after High Tibial Osteotomy in Medial Compartmental Knee Osteoarthritis: Potential Prognostic Biomarkers"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0596-1228","authenticated-orcid":false,"given":"Yoon Hae","family":"Kwak","sequence":"first","affiliation":[{"name":"Division of Orthopaedic Surgery, Severance Children\u2019s Hospital, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dae-Kyung","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8678-2960","authenticated-orcid":false,"given":"Hyun-Soo","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Hallym Institute of Translational Genomics &amp; Bioinformatics, Hallym University Medical Center, Anyang 14068, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Sung","family":"Yee","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0777-1575","authenticated-orcid":false,"given":"Je-Hyun","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.arthro.2010.05.006","article-title":"Open-wedge osteotomy using an internal plate fixator in patients with medial-compartment gonarthritis and varus malalignment: 3-year results with regard to preoperative arthroscopic and radiographic findings","volume":"26","author":"Niemeyer","year":"2010","journal-title":"Arthroscopy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.arthro.2013.02.020","article-title":"Comparative study of medial opening-wedge high tibial osteotomy using 2 different implants","volume":"29","author":"Jung","year":"2013","journal-title":"Arthroscopy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.arthro.2013.10.008","article-title":"Second-look arthroscopic assessment of cartilage regeneration after medial opening-wedge high tibial osteotomy","volume":"30","author":"Jung","year":"2014","journal-title":"Arthroscopy"},{"key":"ref_5","first-page":"555","article-title":"High tibial osteotomy: Indications, techniques, and postoperative management","volume":"64","author":"Prodromos","year":"2015","journal-title":"Instr. Course Lect."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1053\/jars.2002.35258","article-title":"The influences of biomechanical factors on cartilage regeneration after high tibial osteotomy for knees with medial compartment osteoarthritis: Clinical and arthroscopic observation","volume":"18","author":"Kanamiya","year":"2002","journal-title":"Arthroscopy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nrg2290","article-title":"Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight?","volume":"9","author":"Filipowicz","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"e18","DOI":"10.1136\/annrheumdis-2013-204698","article-title":"Signature of circulating microRNAs in osteoarthritis","volume":"74","author":"Beyer","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"12784","DOI":"10.1038\/s41598-017-13104-w","article-title":"Circulating microRNAs: A novel potential biomarker for diagnosing acute aortic dissection","volume":"7","author":"Dong","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1016\/j.joca.2017.03.012","article-title":"A bioinformatic analysis of microRNAs role in osteoarthritis","volume":"25","author":"Cong","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.joca.2016.09.002","article-title":"Utility of circulating serum miRNAs as biomarkers of early cartilage degeneration in animal models of post-traumatic osteoarthritis and inflammatory arthritis","volume":"25","author":"Kung","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.critrevonc.2010.11.004","article-title":"Circulating microRNAs: Association with disease and potential use as biomarkers","volume":"80","author":"Reid","year":"2011","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1016\/j.joca.2017.08.017","article-title":"Changes in biomechanical risk factors for knee osteoarthritis and their association with 5-year clinically important improvement after limb realignment surgery","volume":"25","author":"Birmingham","year":"2017","journal-title":"Osteoarthr. Cartil."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1007\/s00264-017-3517-z","article-title":"Survivorship of medial opening wedge high tibial osteotomy in the elderly: Two to ten years of follow up","volume":"41","author":"Ruangsomboon","year":"2017","journal-title":"Int. Orthop."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100043","DOI":"10.1016\/j.ocarto.2020.100043","article-title":"Assessing in vivo articular cartilage mechanosensitivity as outcome of high tibial osteotomy in patients with medial compartment osteoarthritis: Experimental protocol","volume":"2","author":"Mundermann","year":"2020","journal-title":"Osteoarthr. Cartil. Open"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1177\/0363546518758016","article-title":"Ten-year results of medial open-wedge high tibial osteotomy and chondral resurfacing in severe medial osteoarthritis and varus malalignment","volume":"46","author":"Schuster","year":"2018","journal-title":"Am. J. Sports Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kwak, Y.H., Kwak, D., Kim, N.Y., Kim, Y.J., Lim, J.S., and Yoo, J. (2020). Significant changes in synovial fluid microRNAs after high tibial osteotomy in medial compartmental knee osteoarthritis: Identification of potential prognostic biomarkers. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0227596"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"745","DOI":"10.2106\/00004623-198769050-00016","article-title":"Radiographic analysis of the axial alignment of the lower extremity","volume":"69","author":"Morelanjd","year":"1987","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1111\/jcmm.12927","article-title":"Identification of stably expressed reference small non-coding RNAs for microRNA quantification in high-grade serous ovarian carcinoma tissues","volume":"20","author":"Bignotti","year":"2016","journal-title":"J. Cell. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1007\/s00167-012-2169-1","article-title":"The effects of arthroscopic joint debridement in the knee osteoarthritis: Results of a meta-analysis","volume":"21","author":"Spahn","year":"2013","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1177\/0363546519858996","article-title":"Degree of preoperative subchondral bone marrow lesion is associated with postoperative outcome after medial opening wedge high tibial osteotomy","volume":"47","author":"Kim","year":"2019","journal-title":"Am. J. Sports Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Szwedowski, D., Szczepanek, J., Paczesny, L., Pekala, P., Zabrzynski, J., and Kruczynski, J. (2020). Genetics in cartilage lesions: Basic science and therapy approaches. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155430"},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1016\/j.molonc.2016.10.004","article-title":"Prospective validation of a blood-based 9-miRNA profile for early detection of breast cancer in a cohort of women examined by clinical mammography","volume":"10","author":"Lyng","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_27","first-page":"2852","article-title":"Combination of circulating miR-19b-3p, miR-122-5p and miR-486-5p expressions correlates with risk and disease severity of knee osteoarthritis","volume":"9","author":"Kong","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40001-020-00408-3","article-title":"Clinical significance of miR-19b-3p in patients with sepsis and its regulatory role in the LPS-induced inflammatory response","volume":"25","author":"Xu","year":"2020","journal-title":"Eur. J. Med. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11010-019-03563-2","article-title":"MiR-19b-3p attenuates IL-1\u03b2 induced extracellular matrix degradation and inflammatory injury in chondrocytes by targeting GRK6","volume":"459","author":"Duan","year":"2019","journal-title":"Mol. Cell. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/j.joca.2016.04.019","article-title":"Identification of synovial fluid microRNA signature in knee osteoarthritis","volume":"24","author":"Li","year":"2016","journal-title":"Osteoarthr. Cartil."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13075-019-2086-5","article-title":"Association of circulating microRNAs with prevalent and incident knee osteoarthritis in women: The OFELY study","volume":"22","author":"Rousseau","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"ref_32","first-page":"433","article-title":"Altered function in cartilage derived mesenchymal stem cell leads to OA-related cartilage erosion","volume":"8","author":"Xia","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1302\/2046-3758.611.BJR-2017-0090.R1","article-title":"Dysregulation of both miR-140-39 and miR-140-5p in synovial fluid correlate with osteoarthritis severity","volume":"6","author":"Yin","year":"2017","journal-title":"Bone Jt. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1002\/art.37990","article-title":"Review: The role of microRNAs in osteoarthritis and chondrogenesis","volume":"65","author":"Le","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1002\/jor.21423","article-title":"Assessment of the profiling microRNA expression of differentiated and dedifferentiated human adult articular chondrocytes","volume":"29","author":"Lin","year":"2011","journal-title":"J. Orthop. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1002\/art.24745","article-title":"MicroRNA-140 is expressed in differentiated human articular chondrocytes and modulates interleukin-1 responses","volume":"60","author":"Miyaki","year":"2009","journal-title":"Arthritis Rheum."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4214","DOI":"10.1016\/j.febslet.2006.06.080","article-title":"The cartilage specific microRNA-140 targets histone deacetylase 4 in mouse cells","volume":"580","author":"Tuddenham","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s13148-017-0428-1","article-title":"Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes","volume":"12","author":"Ntoumou","year":"2017","journal-title":"Clin. Epigenetics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1007\/s00394-016-1375-x","article-title":"Epigallocatechin-3-O-gallate modulates global microRNA expression in interleukin-1\u03b2-stimulated human osteoarthritis chondrocytes: Potential role of EGCG on negative co-regulation of microRNA-140-3p and ADAMTS5","volume":"57","author":"Rasheed","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5604\/01.3001.0013.0135","article-title":"miRNA-146a-5p is upregulated in serum and cartilage samples of patients with osteoarthritis","volume":"91","author":"Skrzypa","year":"2019","journal-title":"Pol. Prz. Chir."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13018-017-0542-y","article-title":"MiRNA expression in the cartilage of patients with osteoarthritis","volume":"12","author":"Szala","year":"2017","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1158\/1535-7163.MCT-18-0725","article-title":"miR-454-3p is an exosomal biomarker and functions as a tumor suppressor in glioma","volume":"18","author":"Shao","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"449","DOI":"10.7150\/thno.29055","article-title":"MiR-454-3p-mediated Wnt\/\u03b2-catenin signaling antagonists suppression promotes breast cancer metastasis","volume":"9","author":"Ren","year":"2019","journal-title":"Theranostics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e89656","DOI":"10.1172\/jci.insight.89656","article-title":"Profiling of circulating microRNAs in children with recent onset of type 1 diabetes","volume":"2","author":"Erener","year":"2017","journal-title":"JCI Insight"},{"key":"ref_45","first-page":"A13115","article-title":"Circulating microRNA-454-3p is associated with acute kidney injury in patients with acute decompensated heart failure","volume":"140","author":"Templeton","year":"2019","journal-title":"Genet. Genom."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.clnu.2019.02.042","article-title":"Circulating plasma microRNAs dysregulation and metabolic endotoxemia induced by a high-fat high-saturated diet","volume":"39","author":"Quintanilha","year":"2020","journal-title":"Clin. Nutr."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/2\/258\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:20:50Z","timestamp":1760160050000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/2\/258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,7]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["diagnostics11020258"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11020258","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,7]]}}}