Down-Regulation of microRNA-30d Alleviates Intervertebral Disc Degeneration Through the Promotion of FOXO3 and Suppression of CXCL10

AbstractMicroRNAs (miRNAs/miRs) are important biomarkers for the progression of intervertebral disc degeneration (IDD). We investigated the role of miR-30d in IDD progression through its interactions with forkhead box O3 (FOXO3) and C-X-C motif ligand 10 (CXCL10). We first measured the expression of miR-30d, FOXO3, and CXCL10 in NP cells cultured from IDD patients. RNA-immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were then employed to test the relationship among miR-30d, FOXO3, and CXCL10. Besides, gain- and loss-of function approaches were performed to assess the functional roles of miR-30d and FOXO3 in IDD in vitro and in vivo. We found high expression of miR-30d and CXCL10 and low expression of FOXO3 in IDD. We showed that miR-30d specifically targeted FOXO3, and that down-regulation of miR-30d promoted proliferation and inhibited apoptosis of NP cells in IDD by increasing the expression of FOXO3. Besides, FOXO3 inhibited apoptosis of NP cells by downregulation of CXCL10 expression. Moreover, inhibition of miR-30d promoted proliferation and inhibited apoptosis of NP cells in IDD by decreasing CXCL10. Furthermore, findings in the mouse IDD model confirmed the inhibitory role of decreased miR-30d in IDD progression. Thus, we show that downregulation of miR-30d could promote the proliferation of NP cells by increasing FOXO3 and decreasing CXCL10 expression, which may provide a novel therapeutic target for IDD.

Source: Calcified Tissue International - January 22, 2021 Category: Orthopaedics Source Type: research