Significant Changes in Serum MicroRNAs after High Tibial Osteotomy in Medial Compartmental Knee Osteoarthritis: Potential Prognostic Biomarkers.

ABSTRACT

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.