Abstract
Excessive compression, the main cause of intervertebral disc (IVD) degeneration, affected endogenous repair of the intervertebral disc. Pioglitazone (PGZ) is the agonist of peroxisome proliferator-activated receptor γ, which has been widely used in the treatment of diabetes mellitus. The present study aim at investigating whether pioglitazone has protective effects on compression-mediated cell apoptosis in nucleus pulposus mesenchymal stem cells (NP-MSCs) and further exploring the possible underlying mechanism. Our results indicated that the isolated cells satisfied the criteria of MSC stated by the International Society for Cellular Therapy. Besides, our research revealed that pioglitazone could protect cell viability, cell proliferation of NP-MSCs and alleviated the toxic effects caused by compression. The actin stress fibers was suppressed obviously under compression, and pioglitazone alleviated the adverse outcomes. Pioglitazone exerted protective effects on compression-induced NP-MSCs apoptosis according to annexin V/PI double-staining and TUNEL assays. Pioglitazone suppressed compression-induced NP-MSCs oxidative stress, including decreasing compression-induced overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and alleviated compression-induced mitochondrial membrane potential (MMP) decrease. Ultrastructure collapse of the mitochondria exhibited a notable improvement by pioglitazone in compression-induced NP-MSCs according to transmission electron microscopy (TEM). Furthermore, the molecular results showed that pioglitazone significantly decreased the expression of apoptosis-associated proteins, including cyto.cytochrome c, Bax, cleaved caspase-9, and cleaved caspase-3, and promoted Bcl-2 expression. These results indicated that pioglitazone alleviated compression-induced NP-MSCs apoptosis by suppressing oxidative stress and the mitochondrial apoptosis pathway, which may be a valuable candidate for the treatment of IVD degeneration.
Highlights
Intervertebral disc (IVD) degeneration is a major cause for low back pain (LBP), which has become a global social problem affecting human life and causes a great economic burden on governments [1,2,3]
TUNEL staining revealed that the TUNEL-positive cells were obviously decreased in the pioglitazone group compared with the compression group (Figures 4(c) and 4(d)). These results showed that pioglitazone exerted protective effects on compression-induced nucleus pulposus mesenchymal stem cells (NP-Mesenchymal stem cells (MSCs)) apoptosis
The data showed that pioglitazone significantly reduced MDA which was high in the compression group (Figure 5(c)). These results showed that pioglitazone alleviated compression-induced oxidative stress levels in NP-MSCs
Summary
Intervertebral disc (IVD) degeneration is a major cause for low back pain (LBP), which has become a global social problem affecting human life and causes a great economic burden on governments [1,2,3]. The main therapeutic regimens for IVD degeneration are conservative therapy and surgical decompression of the spine, aimed at Oxidative Medicine and Cellular Longevity alleviating the pain and returning patients to work [4]. Neither of the strategies is effective for treating IVD degeneration. Stem cell therapy has increasingly become a new therapy strategy for the repair of IVD degeneration. Mesenchymal stem cells (MSCs) can differentiate into NP-like cells and promote extracellular matrix (ECM) synthesis, which have exhibited great potential for treating IVD degeneration. Many researches showed that the loss of IVD-MSCs number and function was closely related to IVD degeneration [7, 8]
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