Circ_SPG11 plays contributing effects on IL-1β-induced chondrocyte apoptosis and ECM degradation via miR-665 inhibition-mediated GREM1 upregulation

Abstract

The dysregulation of circular RNA (circRNA) has been monitored in osteoarthritis (OA) cartilage, hinting that circRNA deregulation modulates OA progression. We thus aimed to unveil the role of circRNA spastic paraplegia 11 (circ_SPG11) in OA conditions. The upregulation of circ_SPG11 was observed in OA cartilage and IL-1β-treated chondrocytes. Knockdown of circ_SPG11 restored IL-1β-depleted cell proliferation and alleviated IL-1β-induced cell apoptosis and ECM degradation. Circ_SPG11 bound to miR-665 and negatively regulated miR-665 expression. Inhibition of miR-665 reversed the inhibitory effect on IL-1β-induced chondrocyte injury caused by circ_SPG11 knockdown. GREM1 was a target of miR-665, and circ_SPG11 knockdown depleted GREM1 expression by enriching miR-665. Overexpression of GREM1 also reversed the inhibitory effect on IL-1β-induced chondrocyte injury caused by miR-665 enrichment. Circ_SPG11 might promote IL-1β-induced chondrocyte apoptosis and ECM degradation via increasing GREM1 expression by decoying miR-665.

Keywords: Chondrocyte; GREM1; IL-1β; Osteoarthritis; circ_SPG11; miR-665.