Abstract
The precise role of apoptosis in the pathogenesis of intervertebral disc degeneration (IDD) remains to be elucidated. We analyzed degenerative nucleus pulposus (NP) cells and found that the expression of miR-27a was increased. The overexpression of miR-27a was further verified using real-time RT-PCR. Bioinformatics target prediction identified phosphoinositide-3 kinases (PI3K) as putative targets of miR-27a. Furthermore, miR-27a inhibited PI3K expression by directly targeting their 3’-UTRs, and this inhibition was abolished by mutation of the miR-27a binding sites. Various cellular processes including cell growth, proliferation, migration and adhesion are regulated by activation of the PI3K/AKT signaling pathway, and nucleus pulposus cells are known to strongly express the phosphorylated survival protein AKT. Our results identify PI3K as a novel target of miR-27a. Upregulation of miR-27a thus targets PI3K, initiating apoptosis of nucleus pulposus cells. This present study revealed that downregulated miR-27a might develop a novel intervention for IDD treatment through the prevention of apoptosis in Nucleus pulposus Cells.
Highlights
Intervertebral disc degeneration (IDD) is considered to be the pathological basis of spinal degenerative diseases, which bring a global burden with severe healthcare and socioeconomic costs [1,2]
Compression induces apoptosis of nucleus pulposus (NP) cells To examine the regulatory effect of compression on the growth of NP cells, the MTT assay was used as a measure of cell viability
MiR-27a is up-regulated in damaged NP cells As a multi-functional miRNA, miR-27a is expressed in diverse tissues, and aberrant expression of miR-27a is found to be associated with various diseases
Summary
Intervertebral disc degeneration (IDD) is considered to be the pathological basis of spinal degenerative diseases, which bring a global burden with severe healthcare and socioeconomic costs [1,2]. The mechanisms underlying IDD remain largely unknown, a variety of factors have been suggested to influence its etiology. These include age, genetics, systemic factors and toxins, all of which can affect the balance of biochemical reactions leading to disc degeneration [3,4]. A more recent study showed that NP cells possess distinct characteristics which are necessary for IVD homeostasis [8], while a variety of other studies both in vitro and in vivo suggest that an important contributor to the development of IDD is the cellular loss due to excessive apoptosis of disc cells [9,10]
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