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.