Circular Rna Derived From Timp2 Functions As A Competitive Endogenous Rna And Regulates Intervertebral Disc Degeneration By Targeting Mir-185-5p And Matrix Metalloproteinase 2

Intervertebral disc degeneration (IDD) is an important cause of lower back pain, although the underlying mechanisms remain poorly understood. The present study aimed to examine the role of a circular RNA derived from tissue inhibitor of metallopeptidases 2 (circ-TIMP2) in degenerative nucleus pulposus (NP) tissues, and to validate its function in cultured human NP cells. Overexpression of miR-185-5p in NP cells markedly inhibited the enhanced extracellular matrix (ECM) catabolism induced by tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) treatment. Bioinformatics analysis demonstrated that matrix metalloproteinase 2 (MMP2) was a potential target of miR-185-5p. MMP2 protein expression levels were increased following treatment with TNF-alpha and IL-1 beta in NP cells compared with those in untreated cells, and this effect was attenuated by transfection with miR-185-5p. Compared with normal NP tissues, IDD samples exhibited higher circ-TIMP2 expression levels. In addition, overexpres-sion of circ-TIMP2 promoted ECM catabolism and suppressed ECM anabolism. Furthermore, circ-TIMP2 sequestered miR-185-5p, which may potentially upregulate the target genes associated with ECM degradation. In conclusion, the results of the present study revealed that circ-TIMP2 promoted TNF-alpha- and IL-1 beta-induced NP cell imbalance between ECM anabolism and catabolism via miR-185-5p-MMP2 signaling. These findings provide a potential therapeutic option for the treatment of IDD.