MiRNA Changes after High Tibial Osteotomy and the Mechanism of Knee Osteoarthritis Relive

Abstract

Introduction: This study aimed to observe the changes in miRNA and inflammatory mediators before and after high tibial osteotomy (HTO) and investigate the mechanism of HTO to relieve knee osteoarthritis. Material and Methods: Seventeen cases of patients with arthritis were collected. A synovitis cell model was established by challenging immortalized human synoviocytes (HSs) with lipopolysaccharide (LPS). The weight-bearing line ratio (WBL) values of patients with osteoarthritis before and after HTO surgery were collected. Lubricin, matrix metalloproteinase-1 (MMP-1), monocyte chemoattractant protein-1 (MCP-1) hyaluronic acid (HA), and the concentrations of proinflammatory factors IL (Interleukin)-1β, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α) in the synovial fluid of patients with osteoarthritis before and after surgery were determined using enzyme linked immunosorbent assay (ELISA). miR-23a-3p and miR-30c-5p expression levels in the synovial fluid before and after surgery were measured using quantitative real-time PCR (qRT-PCR). Proliferative activity of HSs was assayed with cell counting kit-8 (CCK-8) proliferation experiment. Results: Proinflammatory cytokines IL-1β, IL-6, IL-8 and TNF-α levels were reduced in the synovial fluid after HTO surgery. Similarly, extracellular matrix proteins, including lubricin and MMP-1 were reduced. In contrast, increased HA, miR-23a-3p, and miR-30c-5p expression levels were observed after HTO surgery, which was accompanied by the recovery of joint function, as revealed by the increased WBL. In the cell model, LPS induction caused the decrease in miR-23a-3p and miR-30c-5p. MiR-23a-3p and miR-30c-5p upregulation rescued the LPS-induction damaging effect on HSs, including cell proliferation capacity and the inflammatory response. Conclusions: These results indicated that HTO ameliorates synovial inflammation and cartilage damage in patients with osteoarthritis. MiR-23a-3p and miR-30c-5p elevated levels may contribute to the beneficial effect of HTO treatment on osteoarthritis by attenuating inflammatory responses in knee joints.