Background: Total joint replacement for osteoarthritis is one of the most successful surgical procedures in modern medicine. However, aseptic loosening continues to be a leading cause of revision arthroplasty. The diagnosis of aseptic loosening remains a challenge as patients are often asymptomatic until the late stages. MicroRNA (miRNA) has been demonstrated to be a useful diagnostic tool and has been successfully used in the diagnosis of other diseases. We aimed to identify differentially expressed miRNA in the plasma of patients with aseptic loosening.
Methods: Adult patients undergoing revision arthroplasty for aseptic loosening and age- and gender-matched controls were recruited. Samples of bone, tissue and blood were collected, and RNA sequencing was performed in 24 patients with aseptic loosening and 26 controls. Differentially expressed miRNA in plasma was matched to differentially expressed mRNA in periprosthetic bone and tissue. Western blot was used to validate protein expression.
Results: Seven miRNA was differentially expressed in the plasma of patients with osteolysis (logFC >|2|, adj-P < 0.05). Three thousand six hundred and eighty mRNA genes in bone and 427 mRNA genes in tissue samples of osteolysis patients were differentially expressed (logFC >|2|, adj-P < 0.05). Gene enrichment analysis and pathway analysis revealed two miRNA (miR-1246 and miR-6089) had multiple gene targets in the Wnt signalling pathway in the local bone and tissues which regulate bone metabolism.
Conclusion: These results suggest that aseptic loosening may be regulated by miR-1246 and miR-6089 via the Wnt signalling pathway.
Keywords: Aseptic loosening; MicroRNA; Revision surgery; Sequencing; Wnt pathway.
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