Significant changes in synovial fluid microRNAs after high tibial osteotomy in medial compartmental knee osteoarthritis: Identification of potential prognostic biomarkers

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 6month SF samples (p = 0.006 and 0.007, respectively). Of these two miRNAs, miR-30c-5p

Molecular mechanisms of mechanical load-induced osteoarthritis

“…Numerous studies have reported that mechanical loading causes differential expression of microRNA (MIRNA) in articular cartilage and regulates the levels of matrix-degrading enzymes and inflammatory factors in osteoarthritis cartilage [54]. Specifically, it targets the expression of downstream transcripts.…”

Xanthohumol Inhibited Mechanical Stimulation-Induced Articular ECM Degradation by Mediating lncRNA GAS5/miR-27a Axis

“…Transforming growth factor-β (TGF-β) maintains functions of articular cartilage by transducing Smad2/3 signals, thereby promoting collagen (Col2a1) and fibronectin synthesis and inhibiting ECM degradation induced by overloading ( Madej et al, 2016 ). Mechanical loading also causes differential expression of miRNAs ( Kwak et al, 2020 ) and lncRNAs ( He et al, 2021 ), which regulate the activities of MMPs and the progress of OA development.…”

Osteoarthritis year in review: genetics, genomics, epigenetics

“…This year, advances in single cell technologies were used to profile cell surface markers and disease associated subsets. Recently, Dicks et al were found to be associated with post-operative pain outcomes [35,36]. The identification of these candidates is an important first step, however to have any clinical utility they must be validated in multiple cohorts, with larger sample sizes.…”