A novel mechanism for the protection of embryonic stem cell derived tenocytes from inflammatory cytokine interleukin 1 beta.
Alyce McClellanRichard EvansCheryl SzeShohei KanYasmin PatersonDeborah J GuestPublished in: Scientific reports (2019)
Interleukin 1β (IL-1β) is upregulated following tendon injury. Here we demonstrate that in adult and fetal tenocytes IL-1β increases the expression of matrix metalloproteinases, tenascin-C and Sox9 and decreases the expression of scleraxis and cartilage oligomeric matrix protein. When cultured in 3-dimensional collagen gels adult and fetal tenocytes exposed to IL-1β have reduced contraction ability and generate tendon-like constructs with a lower storage modulus. In contrast, equine embryonic stem cell (ESC) derived tenocytes exposed to IL-1β exhibit no changes in gene expression and generate identical tendon-like constructs. We propose that ESC-derived tenocytes do not respond to IL-1β due to their low expression of interleukin 1 (IL-1) receptor 1 and high expression of the decoy receptor IL-1 receptor 2 and IL-1 receptor antagonist protein (IL1Ra). This may make ESC-derived tenocytes an advantageous source of cells for tissue regeneration and allow the development of novel pharmaceutical interventions to protect endogenous cells from inflammation.
Keyphrases
- stem cells
- poor prognosis
- gene expression
- binding protein
- oxidative stress
- magnetic resonance
- rheumatoid arthritis
- long non coding rna
- endothelial cells
- systemic lupus erythematosus
- cell proliferation
- mesenchymal stem cells
- physical activity
- bone marrow
- computed tomography
- extracellular matrix
- anterior cruciate ligament reconstruction
- rotator cuff
- childhood cancer