Autophagy Modulation in Osteoarthritis Pathogenesis

Osteoarthritis is characterised by progressive cartilage degradation, subchondral bone remodelling and synovial inflammation. Central to these processes is the balance between anabolic and catabolic pathways within chondrocytes, the sole cell type in articular cartilage. Autophagy, a conserved intracellular degradation system, maintains cellular homeostasis by removing damaged organelles and protein aggregates. In osteoarthritis, dysregulation of autophagy contributes to chondrocyte apoptosis, extracellular matrix breakdown and amplified inflammatory signalling. Modulation of key autophagy regulators such as the mammalian target of rapamycin (mTOR) and transcription factor EB (TFEB) has been shown to restore autophagic flux, preserve mitochondrial function and blunt endoplasmic reticulum stress. Collectively, these insights underscore autophagy as both a pathogenic mechanism and a therapeutic target, with interventions ranging from small-molecule mTOR inhibitors to gene- and miRNA-based approaches aiming to revive autophagic competence in diseased cartilage.

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Autophagy Modulation in Osteoarthritis Pathogenesis publication trend

The graph below shows the total number of articles in autophagy modulation in osteoarthritis pathogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Autophagy: A cellular process for degrading and recycling damaged organelles and proteins through lysosomal pathways.

Autophagic flux: The dynamic process of autophagosome formation, maturation and degradation that reflects the functional status of autophagy.

Chondrocyte: The specialised cell type responsible for the synthesis and maintenance of cartilage extracellular matrix.

mTOR (mammalian target of rapamycin): A serine/threonine kinase that negatively regulates autophagy in response to nutrient and growth factor signals.

Exosome: A small extracellular vesicle released by cells that can transfer proteins, lipids and nucleic acids to modulate recipient cell functions.

References

1. Engineering exosomes derived from subcutaneous fat MSCs specially promote cartilage repair as miR-199a-3p delivery vehicles in Osteoarthritis. Journal of Nanobiotechnology (2023).
2. Autophagy in the pathogenesis and therapeutic potential of post-traumatic osteoarthritis. Burns & Trauma (2023).
3. Identification of autophagy-related genes in osteoarthritis articular cartilage and their roles in immune infiltration. Frontiers in Immunology (2023).
4. Local intra-articular injection of rapamycin delays articular cartilage degeneration in a murine model of osteoarthritis. Arthritis Research & Therapy (2014).
5. Trehalose ameliorates oxidative stress-mediated mitochondrial dysfunction and ER stress via selective autophagy stimulation and autophagic flux restoration in osteoarthritis development. Cell Death & Disease (2017).
6. TFEB, a potential therapeutic target for osteoarthritis via autophagy regulation. Cell Death & Disease (2018).