Related Experiment Video
Updated: Apr 23, 2026
Matrix-assisted Autologous Chondrocyte Transplantation for Remodeling and Repair of Chondral Defects in a Rabbit Model
Published on: May 21, 2013
Advanced glycation end products-induced chondrocyte apoptosis through mitochondrial dysfunction in cultured rabbit
Qingshan Yang1, Shifang Guo, Song Wang
1Department of Orthopaedics, Gan Su Province Hospital, Lan Zhou, 73000, China.
Abstract:
Advanced glycation end products (AGEs) are an important mediator in osteoarthritis (OA) and cause apoptosis in articular chondrocytes. Mitochondrial function is involved in modulating apoptosis of articular chondrocytes. This study was performed to investigate the mechanism of AGEs-induced chondrocyte apoptosis. The ratio of apoptotic cell and cell viability was surveyed by TUNEL, MTT,LDH release assay. The reactive oxygen species was determined by the fluorescent probe 2', 7'-dichlorofluorescein diacetate. The expression of caspase-3 and cytochrome c was detected by Western blot. The mitochondrial membrane potential (▵Ψm) was evaluated by rhodamine-123 fluorescence. We found that AGEs induced apoptosis in primary rabbit chondrocytes, upregulation of ROS production, cytochrome c, and caspase-3 levels. Simultaneously, AGEs decreases the levels of ▵Ψm and ATP production; however, the antibody of AGEs (sRAGE) and antioxidant-N-acetylcys-teine (NAC) significantly reversed AGEs-induced the above damage thus to protect the cells from apoptosis. These observations suggested that the mechanism of AGEs-induced chondrocyte apoptosis was primarily via ROS production and mitochondria-mediated caspase-3 activation.
Insights
Advanced glycation end products (AGEs) induce osteoarthritis (OA) by causing chondrocyte apoptosis. AGEs trigger reactive oxygen species (ROS) and activate caspase-3 through mitochondrial pathways, leading to cartilage damage.
Area of Science:
- Biochemistry
- Cell Biology
- Biomedical Engineering
Background:
- Advanced glycation end products (AGEs) are implicated in osteoarthritis (OA) pathogenesis.
- AGEs contribute to articular chondrocyte apoptosis, a key process in OA.
- Mitochondrial dysfunction plays a role in chondrocyte apoptosis.
Purpose of the Study:
- To investigate the precise mechanism by which AGEs induce apoptosis in articular chondrocytes.
- To elucidate the role of mitochondrial function and reactive oxygen species (ROS) in AGEs-induced chondrocyte apoptosis.
Main Methods:
- TUNEL, MTT, and LDH release assays were used to assess chondrocyte apoptosis and viability.
- Reactive oxygen species (ROS) production was quantified using a fluorescent probe.
- Western blot analysis detected caspase-3 and cytochrome c expression.
- Mitochondrial membrane potential (ΔΨm) was evaluated using rhodamine-123 fluorescence.
Main Results:
- AGEs exposure led to increased chondrocyte apoptosis, ROS production, and elevated levels of cytochrome c and caspase-3.
- AGEs significantly decreased mitochondrial membrane potential (ΔΨm) and ATP production.
- Treatment with an AGEs antibody (sRAGE) or the antioxidant N-acetylcysteine (NAC) reversed these AGEs-induced effects, protecting chondrocytes.
Conclusions:
- AGEs induce articular chondrocyte apoptosis primarily through ROS generation.
- The mechanism involves mitochondria-mediated activation of caspase-3.
- Targeting ROS and mitochondrial pathways may offer therapeutic strategies for osteoarthritis.
