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Osteoarthritis (OA) is a highly prevalent joint disorder that is tightly correlated with age. As the body ages, cell replication and function decline until homeostasis can no longer be maintained. This process involves cellular senescence as well as replicative senescence. Telomere length, cell cycle arrest, expression of p16 and p53, and the release of senescence-associated β-galactosidase (SA-β-Gal) are all markers of cell senescence. In OA joints, chondrocytes undergo cellular senescence prematurely, thereby ceasing to synthesize and maintain cartilage tissue. Upregulation of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), and oxidative stress induced by overproduction of reactive oxygen species (ROS) are key events in the pathogenesis of OA. In the present study, we investigated the effects of pinitol, a naturally occurring compound, on the effects of TNF-α on chondrocyte senescence and cell cycle arrest. We found that pinitol has a favorable safety profile in terms of cell viability. Pinitol significantly inhibited cellular senescence and cell cycle arrest in the G0/G1 phase induced by TNF-α. We also found that pinitol could inhibit TNF-α-induced increased telomerase activity and expression of p16 and p53. Importantly, we found that the effects of pinitol may be mediated through rescue of Nrf2 signaling, which is recognized as a key protective factor in OA. This finding was verified through a Nrf2 silencing experiment using Nrf2 siRNA. Together, our findings reveal the potential of pinitol as a safe therapeutic option for the prevention of OA-associated chondrocyte senescence and oxidative stress.
This article was published in the following journal.
Microglia-involved neuroinflammation in the central nervous system (CNS) has been shown to aggravate brain damage and is associated with the pathogenesis of various neurodegenerative diseases. Thus, s...
Arsenic-contaminated drinking water is known to be a serious human health problem. A previous epidemiological study has indicated that arsenic levels in blood were higher in arthritis patients compare...
Arsenic is awfully toxic metalloid responsible for many human diseases all over the world. Contrastingly, D-pinitol is a naturally occurring bioactive dietary compound has antioxidant properties. The ...
Following a specific number of mitotic divisions, primary chondrocytes undergo proliferative senescence, thwarting efforts to expand sufficient populations in vitro suitable to meet the needs of scien...
Cellular Senescence is associated with organismal aging and related pathologies. Previously, we reported that plasminogen activator inhibitor-1 (PAI-1) is an essential mediator of senescence and a pot...
The aim of the study is to investigate the impact of Anti-Thymocyte Globulin (ATG) on immune senescence. Markers of immune senescence expression is assessed in a prospective cohort of rena...
The purpose of this study is to measure the outcomes of patients who have articular cartilage lesions in the patellofemoral joint and are treated with the Autologous Chondrocyte Implantati...
Circulatory shocks (CS) are life-threatening, acute organ dysfunction. Advances in critical care medicine have decreased early hospital mortality, increasing the number of surviving patien...
A clinical trial to evaluate the long-term efficacy and safety of a CHONDRON (Autologous cultured Chondrocyte) for 48weeks, and additional 96weeks in patients with cartilage defects in the...
Patients with cancer often complain that their "mind does not seem to be clear." This can be due to stress, depression, anxiety, or physical problems caused by cancer or the treatments use...
Process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing CELL DEATH. Senescence can be induced by DNA DAMAGE or other cellular stresses, such as OXIDATIVE STRESS.
Abnormally high temperature intentionally induced in living things regionally or whole body. It is most often induced by radiation (heat waves, infra-red), ultrasound, or drugs.
A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.
Artificially induced UTERINE CONTRACTION. Generally, LABOR, OBSTETRIC is induced with the intent to cause delivery of the fetus and termination of pregnancy.
A treatment that suppresses undesirable behavior by simultaneously exposing the subject to unpleasant consequences.
Cytokine Tumour Necrosis Factor (TNF)
TNF is a compound that is classified as a cytokine which plays a central role in the cellular mechanisms of apoptosis or cell death. However, there are a number of different kinds of TNF, just under twenty, but the family of molecules have very similar a...
Arthritis Fibromyalgia Gout Lupus Rheumatic Rheumatology is the medical specialty concerned with the diagnosis and management of disease involving joints, tendons, muscles, ligaments and associated structures (Oxford Medical Diction...