Abstract
Objective To investigate the role of PI3K/AKT signaling pathway in nucleus pulposus (NP) cells. Methods Nucleus pulposus (NP) cells were isolated from SD rat, and thereafter, passage three (P3) NP cells were divided into the following experimental groups: control, PI3K/AKT agonist IGF-1 (25 ng/ml, 50 ng/ml, and 100 ng/ml), and PI3K/AKT inhibitor LY294002 (5 μM, 10 μM, and 20 μM). Flow cytometry and BrdU cell proliferation assays were performed to assess apoptosis and the proliferation rate of NP cells. Western blot analysis was performed to examine the protein expression level of Col II, Col X, Aggrecan, and MMP13. Results PI3K/AKT inhibitor LY294002 increased the rate of apoptosis in NP cells when compared to the control and decreased the proliferation rate when compared to control. Moreover, LY294002 decreased the protein expression level of Col-II and Aggrecan in NP cells. At the same time, LY294002 increased the protein expression level of MMP13 and Col-X in NP cells. Through activating PI3K/AKT, IGF-1 increased the proliferation rate when compared to control and decreased the rate of apoptosis when compared to control. Additionally, IGF-1 decreased the protein expression level of MMP13 and Col-X and increased Col-II and Aggrecan in NP cells. Conclusion The inhibition of PI3K/AKT signaling pathway accelerated the apoptosis of NP cells and facilitated the extracellular matrix degradation. However, the activation of PI3K/AKT pathway partly prevented the NP cell from apoptosis and promoted their proliferation. Meanwhile, its activation also delayed the loss of extracellular matrix.
Highlights
Intervertebral disc degeneration (IDD) is the main cause of lumbar disc herniation, spinal stenosis, and spondylolisthesis [1]
We speculated that the PI3K/AKT signaling pathway might be involved in the degeneration of nucleus pulposus (NP) cells which in turn result in IDD
A mass of studies has identified the aberrant transcription of genes which may activate or block PI3K/AKT pathway are related to the degenerated NPCs in IDD patients
Summary
Intervertebral disc degeneration (IDD) is the main cause of lumbar disc herniation, spinal stenosis, and spondylolisthesis [1]. It severely affects public health and leads to a heavy economic burden on the society, which urges us to understand the pathogenic mechanism of IDD and find novel therapies [2]. NP cells as the main components of the nucleus pulposus are responsible for the production and maintenance of extracellular matrix (ECM) containing collagen fibres and variety of proteoglycans especially aggrecan bearing compressive loads [4]. It is generally believed that IDD is partly caused due to the depletion of NP cells and degradation of ECM [5].
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