Abstract
Intervertebral disc degeneration (IVDD) is the primary cause of low back pain; however, the molecular mechanisms involved in the pathogenesis of IVDD are not fully understood. Polo-like kinase 1 (PLK1) plays numerous roles in the cell cycle, including in cell proliferation and senescence. To investigate the involvement of PLK1 in IVDD, we used patient tissues and an animal model of IVDD. Samples were analyzed via immunoblotting, quantitative real-time polymerase chain reaction (qPCR), immunofluorescence, and immunohistochemistry. Our results demonstrated that PLK1 expression was decreased in nucleus pulposus cells (NPCs) of degenerative IVDs. The inhibition of PLK1 kinase activity in normal NPCs increased the expression of p53 protein, inhibited cell proliferation, and induced senescence. Our results suggest that PLK1 regulates the degeneration of the IVD through p53, revealing the function and mechanism of PLK1 in IVDD and providing a theoretical basis and experimental evidence for the potential treatment of low back pain.
Highlights
Low back pain (LBP) is one of major disabilities worldwide, currently affecting approximately 632 million people (Andersson, 1999; Vos et al, 2012)
It has been established that the pathogenesis of IVDD is a very complex process initiated by several factors, including aging, Abbreviations: IVD, intervertebral disc; IVDD, intervertebral disc degeneration; NPC, nucleus pulposus cells; LBP, low back pain; matrix metalloproteinases (MMPs), metalloproteinase; PG, proteoglycan; ECM, extracellular matrix
Polo-like kinase 1 (PLK1) Expression is Decreased in NPCs in IVDD
Summary
Low back pain (LBP) is one of major disabilities worldwide, currently affecting approximately 632 million people (Andersson, 1999; Vos et al, 2012). It has been established that the pathogenesis of IVDD is a very complex process initiated by several factors, including aging, Abbreviations: IVD, intervertebral disc; IVDD, intervertebral disc degeneration; NPC, nucleus pulposus cells; LBP, low back pain; MMP, metalloproteinase; PG, proteoglycan; ECM, extracellular matrix. PLK1 in Intervertebral Disc Degeneration tissue samples, the levels of type II collagen and proteoglycan (PG) are reduced (Lyons et al, 1981), whereas the expression levels of MMPs and second family of metalloproteinases (ADAMs), such as ADAMTS4 and 5 (Liu et al, 1991; Roughley, 2004) are increased. The synthesis of extracellular matrix (ECM) (PG and type II collagen) is markedly decreased, and the hydration of the intervertebral disc ECM is reduced, further aggravating the degeneration of NP cells (NPCs) (Hoyland et al, 2008)
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