MicroRNA-10b Promotes Nucleus Pulposus Cell Proliferation through RhoC-Akt Pathway by Targeting HOXD10 in Intervetebral Disc Degeneration

Abstract

Aberrant proliferation of nucleus pulposus cell is implicated in the pathogenesis of intervertebral disc degeneration. Recent findings revealed that microRNAs, a class of small noncoding RNAs, could regulate cell proliferation in many pathological conditions. Here, we showed that miR-10b was dramatically upregulated in degenerative nucleus pulposus tissues when compared with nucleus pulposus tissues isolated from patients with idiopathic scoliosis. Moreover, miR-10b levels were associated with disc degeneration grade and downregulation of HOXD10. In cultured nucleus pulposus cells, miR-10b overexpression stimulated cell proliferation with concomitant translational inhibition of HOXD10 whereas restored expression of HOXD10 reversed the mitogenic effect of miR-10b. MiR-10b-mediated downregulation of HOXD10 led to increased RhoC expression and Akt phosphorylation. Either knockdown of RhoC or inhibition of Akt abolished the effect of miR-10b on nucleus pulposus cell proliferation. Taken together, aberrant miR-10b upregulation in intervertebral disc degeneration could contribute to abnormal nucleus pulposus cell proliferation through derepressing the RhoC-Akt pathway by targeting HOXD10. Our study also underscores the potential of miR-10b and the RhoC-Akt pathway as novel therapeutic targets in intervertebral disc degeneration.

Dysregulated miR-98 Contributes to Extracellular Matrix Degradation by Targeting IL-6/STAT3 Signaling Pathway in Human Intervertebral Disc Degeneration

“…There is an age gap between patients and controls in this study. As in previous studies concerning the role of miRNA in IDD, (21,22,38) an age gap between patients and controls was also observed. However, the effect of age gap on miRNA levels was not investigated.…”

“…(19,20) Of note, miRNAs have been implicated in apoptosis of nucleus pulposus (NP) cells, control of NP cell proliferation, and collagen loss in NP cell. (21)(22)(23) Here, we sought to understand the role of miRNAs in IL-6-induced IDD. NP cells play an important role in maintaining the integrity of the intervertebral disc through their role in producing type II collagen, aggrecan, and other components of ECM.…”

Adolescent idiopathic scoliosis: evidence for intrinsic factors driving aetiology and progression

“…Furthermore, there may be much to learn from studies that have examined the molecular basis for intervertebral disc degeneration in nonidiopathic scoliosis patient samples, where aberrant proliferation of cells in the nucleus pulposus is also implicated in the pathogenesis. Recent studies have reported that the noncoding micro-RNAs miR-10b and miR-21 can both promote nucleus pulposus cellular proliferation via inhibition of protein kinase B (AKT) signalling pathways [32,67]. Both miR-10b and miR-21 expression were reported to be higher in nucleus pulposus tissue from patients with identified intervertebral disc degeneration compared with nucleus pulposus tissue from patients with idiopathic scoliosis.…”

Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods

“…By contrast, microRNAs (miRNAs) that can regulate RNA degradation or repression of translation have been identified as key regulators in numerous biological processes (16). Recently, Yu et al (17) demonstrated that miR-10b could promote nucleus pulposus cell proliferation by targeting homeobox D10 through the ras homolog family member C-Akt pathway in IDD. However, the molecular mechanism of IDD is not fully understood and further investigations are required.…”