Promising targets for therapy of osteoarthritis: a review on the Wnt and TGF-β signalling pathways.
Chahrazad CherifiSilvia MonteagudoRik Ju LoriesPublished in: Therapeutic advances in musculoskeletal disease (2021)
Osteoarthritis (OA) is the most common chronic joint disorder worldwide, with a high personal burden for the patients and an important socio-economic impact. Current therapies are largely limited to pain management and rehabilitation and exercise strategies. For advanced cases, joint replacement surgery may be the only option. Hence, there is an enormous need for the development of effective and safe disease-modifying anti-OA drugs. A strong focus in OA research has been on the identification and role of molecular signalling pathways that contribute to the balance between anabolism and catabolism in the articular cartilage. In this context, most insights have been gained in understanding the roles of the transforming growth factor-beta (TGF-β) and the Wingless-type (Wnt) signalling cascades. The emerging picture demonstrates a high degree of complexity with context-dependent events. TGF-β appears to protect cartilage under healthy conditions, but shifts in its receptor use and subsequent downstream signalling may be deleterious in aged individuals or in damaged cartilage. Likewise, low levels of Wnt activity appear important to sustain chondrocyte viability but excessive activation is associated with progressive joint damage. Emerging clinical data suggest some potential for the use of sprifermin, a recombinant forms of fibroblast growth factor 18, a distant TGF-β superfamily member, and for lorecivivint, a Wnt pathway modulator.
Keyphrases
- transforming growth factor
- epithelial mesenchymal transition
- pain management
- knee osteoarthritis
- cell proliferation
- stem cells
- end stage renal disease
- rheumatoid arthritis
- chronic kidney disease
- ejection fraction
- newly diagnosed
- minimally invasive
- multiple sclerosis
- oxidative stress
- extracellular matrix
- high intensity
- peritoneal dialysis
- coronary artery disease
- patient reported outcomes
- risk assessment
- cell therapy
- big data
- coronary artery bypass
- body mass index
- single molecule
- artificial intelligence
- human health
- machine learning
- acute coronary syndrome
- atrial fibrillation