The effect of tranexamic acid on synovium of patients undergoing arthroplasty and anterior cruciate ligament reconstruction surgery

Naunyn Schmiedebergs Arch Pharmacol. 2023 Dec;396(12):3733-3742. doi: 10.1007/s00210-023-02555-w. Epub 2023 Jun 15.

Abstract

Preoperative hemorrhage can be reduced using anti-fibrinolytic medicine tranexamic acid (TXA). During surgical procedures, local administration is being used more and more frequently, either as an intra-articular infusion or as a perioperative rinse. Serious harm to adult soft tissues can be detrimental to the individual since they possess a weak ability for regeneration. Synovial tissues and primary fibroblast-like synoviocytes (FLS) isolated from patients were examined using TXA treatment in this investigation. FLS is obtained from rheumatoid arthritis (RA), osteoarthritis (OA), and anterior cruciate ligament (ACL)-ruptured patients. The in vitro effect of TXA on primary FLS was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays for cell death, annexin V/propidium iodide (PI) staining for apoptotic rate, real-time PCR for p65 and MMP-3 expression, and enzyme-linked immunosorbent assay (ELISA) for IL-6 measurement. MTT assays revealed a significant decrease in cell viability in FLS of all groups of patients following treatment with 0.8-60 mg/ml of TXA within 24 h. There was a significant increase in cell apoptosis after 24 h of exposure to TXA (15 mg/ml) in all groups, especially in RA-FLS. TXA increases the expression of MMP-3 and p65 expression. There was no significant change in IL-6 production after TXA treatment. An increase in receptor activator of nuclear factor kappa-Β ligand (RANK-L) production was seen only in RA-FLS. This study demonstrates that TXA caused significant synovial tissue toxicity via the increase in cell death and elevation of inflammatory and invasive gene expression in FLS cells.

Keywords: Arthroplasty; Fibroblast-like synoviocytes; Synovium; Toxicity; Tranexamic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anterior Cruciate Ligament Reconstruction*
  • Arthritis, Rheumatoid*
  • Arthroplasty
  • Cells, Cultured
  • Fibroblasts / metabolism
  • Humans
  • Interleukin-6 / metabolism
  • Matrix Metalloproteinase 3 / metabolism
  • Synovial Membrane / metabolism
  • Tranexamic Acid* / metabolism
  • Tranexamic Acid* / pharmacology

Substances

  • Tranexamic Acid
  • Matrix Metalloproteinase 3
  • Interleukin-6