Abstract
High tibial osteotomy (HTO) is a well-established treatment for medial compartmental knee osteoarthritis. Several microRNAs (miRNAs) are involved in osteoarthritis progression and are useful as osteoarthritis-related biomarkers. In this prospective study, we investigated differentially expressed microRNAs in the synovial fluid (SF) before and after HTO in patients with medial compartmental knee osteoarthritis to identify microRNAs that can be used as prognostic biomarkers. We used miRNA-PCR arrays to screen for miRNAs in SF samples obtained preoperatively and 6 months postoperatively from 6 patients with medial compartmental knee osteoarthritis who were treated with medial open wedge HTO. Differentially expressed miRNAs identified in the profiling stage were validated by real-time quantitative PCR in 22 other patients who had also been treated with HTO. All patients radiographically corresponded to Kellgren-Lawrence grade II or III with medial compartmental osteoarthritis. These patients were clinically assessed using a visual analogue scale and Western Ontario McMaster Universities scores. Mechanical axis changes were measured on standing anteroposterior radiographs of the lower limbs assessed preoperatively and at 6 months postoperatively. Among 84 miRNAs known to be involved in the inflammatory process, 14 were expressed in all SF specimens and 3 (miR-30a-5p, miR-29a-3p, and miR-30c-5p) were differentially expressed in the profiling stage. These 3 miRNAs, as well as 4 other miRNAs (miR-378a-5p, miR-140-3p, miR-23a-3p, miR-27b-3p), are related to osteoarthritis progression. These results were validated in the SF from 22 patients. Clinical and radiological outcomes improved after HTO in all patients, and only 2 miRNAs (miR-30c-5p and miR-23a-3p) were significantly differentially expressed between preoperative and postoperative 6-month SF samples (p = 0.006 and 0.007, respectively). Of these two miRNAs, miR-30c-5p correlated with postoperative pain relief. This study provides potential prognostic miRNAs after HTO and further investigations should be considered to determine clinical implications of these miRNAs.
Highlights
High tibial osteotomy (HTO) is a well-known treatment modality for active patients with medial compartmental osteoarthritis (OA) of the knee [1,2]
The expression results for the 84 miRNAs based on biological groups are shown in a heat map (Fig 2), and the PCR array analysis revealed 14 of the 84 target miRNAs in all synovial fluid (SF) specimens
3 miRNAs, miR-30a-5p, miR-29a-3p, and miR-30c-5p, were upregulated with a significant fold change, and these were included in the validation testing (Table 3)
Summary
High tibial osteotomy (HTO) is a well-known treatment modality for active patients with medial compartmental osteoarthritis (OA) of the knee [1,2]. Several studies have shown a correlation between HTO and regeneration of the degenerated cartilage, which is thought to occur through the realignment of the mechanical axis in medial compartmental knee OA. Regeneration of the degenerated articular cartilage in the medial compartment in medial compartmental knee OA can be expected following HTO without the need for any additional procedures, the detailed mechanism is still unclear. Any changes in miRNA expression in the synovial fluid (SF) could be related to the change in the MA following HTO and subsequent cartilage regeneration. These miRNAs could be used as biomarkers to predict the prognosis after HTO. This prospective study was conducted to determine which miRNAs in the SF are significantly differentially expressed after HTO for medial compartment knee OA and to identify the miRNAs that can serve as biomarkers related to overall prognosis
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