New developments in chondrocyte ER stress and related diseases.
Michael D BriggsElla P DennisHelen F DietmarKatarzyna Anna PirógPublished in: F1000Research (2020)
Cartilage comprises a single cell type, the chondrocyte, embedded in a highly complex extracellular matrix. Disruption to the cartilage growth plate leads to reduced bone growth and results in a clinically diverse group of conditions known as genetic skeletal diseases (GSDs). Similarly, long-term degradation of articular cartilage can lead to osteoarthritis (OA), a disease characterised by joint pain and stiffness. As professionally secreting cells, chondrocytes are particularly susceptible to endoplasmic reticulum (ER) stress and this has been identified as a core disease mechanism in a group of clinically and pathologically related GSDs. If unresolved, ER stress can lead to chondrocyte cell death. Recent interest has focused on ER stress as a druggable target for GSDs and this has led to the first clinical trial for a GSD by repurposing an antiepileptic drug. Interestingly, ER stress markers have also been associated with OA in multiple cell and animal models and there is increasing interest in it as a possible therapeutic target for treatment. In summary, chondrocyte ER stress has been identified as a core disease mechanism in GSDs and as a contributory factor in OA. Thus, chondrocyte ER stress is a unifying factor for both common and rare cartilage-related diseases and holds promise as a novel therapeutic target.
Keyphrases
- extracellular matrix
- clinical trial
- cell death
- knee osteoarthritis
- endoplasmic reticulum
- cell cycle arrest
- induced apoptosis
- chronic pain
- rheumatoid arthritis
- single cell
- randomized controlled trial
- pain management
- genome wide
- spinal cord
- copy number
- bone mineral density
- drug induced
- soft tissue
- mesenchymal stem cells
- bone marrow
- cell proliferation
- signaling pathway
- phase ii
- replacement therapy