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Oxidative stress, autophagy, epigenetic changes and regulation by miRNAs as potential therapeutic targets in osteoarthritis
- Source :
- Biochemical Pharmacology. 108:1-10
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Aging is a natural process characterized by the declining ability of the different organs and tissues to respond to stress, increasing homeostatic imbalance and risk of disease. Osteoarthritis (OA) is a multifactorial disease in which cartilage degradation is a central feature. Aging is the main risk factor for OA. In OA cartilage, a decrease in the number of chondrocytes and in their ability to regenerate the extracellular matrix and adequately respond to stress has been described. OA chondrocytes show a senescence secretory phenotype (SSP) consisting on the overproduction of cytokines (interleukins 1 and 6), growth factors (e.g., epidermal growth factor) and matrix metalloproteinases (MMP) (e.g., MMP-3, MMP-13). Reactive Oxygen Species (ROS) play a major role in the induction of the SSP. In chondrocytes, an increase in ROS production leads to hyper-peroxidation, protein carbonylation and DNA damage which alter chondrocyte function. ROS overproduction also induces changes in metabolic pathways such as PI3K-Akt and ERK. Autophagy is a key mechanism for maintaining cell homeostasis by adjusting cell metabolism to nutrient supply and removing damaged organelles. In cartilage, aging-related loss of autophagy leads to cell death and OA, while stimulation of autophagy exerts protective effects on cartilage deterioration. Aging also interferes with epigenetic mechanisms such as activity of histone acetylases that control the pattern of DNA methylation, and induces up- or down-regulation of microRNAs expression. A deeper knowledge of the mechanisms involved in chondrocyte aging could identify potential targets for the treatment of OA, a prevalent and therapeutic-orphan disease.
- Subjects :
- 0301 basic medicine
Senescence
MAPK/ERK pathway
Aging
Programmed cell death
DNA damage
Biology
medicine.disease_cause
Biochemistry
Chondrocyte
Epigenesis, Genetic
03 medical and health sciences
Chondrocytes
Osteoarthritis
Autophagy
medicine
Animals
Humans
Molecular Targeted Therapy
Epigenetics
Cellular Senescence
Pharmacology
DNA Methylation
Cell biology
MicroRNAs
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
Immunology
Reactive Oxygen Species
Oxidative stress
DNA Damage
Subjects
Details
- ISSN :
- 00062952
- Volume :
- 108
- Database :
- OpenAIRE
- Journal :
- Biochemical Pharmacology
- Accession number :
- edsair.doi.dedup.....6c7772c82fbd4f45f6c380c4bfac9cea