New drugs targeting Wnt pathway may assist bone healing

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Scientists based at the University of Southampton are in the process of developing new drugs to aid bone healing. Their research has identified the Wnt pathway, a highly conserved signalling pathway found from sponges to mammals, as an important player in bone stem cell regeneration.

From fractures to hip replacements, bone damage can come in many forms; in many patients however, this damage can become a long-term problem. Doctor Nick Evans, lead author of the study and Associate Professor in Bioengineering at the University of Southampton, explained; “Bone fractures are a big problem in society, especially in older people. It is getting worse as more people get older and their risk of fracture increases. Most fractures heal completely by themselves, but a surprising number, around 10 per cent, take over six months to heal, or never heal at all. In the worst cases this can lead to several surgical operations, or even amputation.”

Previous research has suggested that activation of Wnt signaling can promote the build-up of minerals in patients with osteoporosis, a disease characterised by an absence of minerals within the bone structure. Evans and his team were interested in whether activation on the pathway would also have beneficial effects in bones damaged by fracture, so they isolated bone marrow mononuclear cells (BMMNCs) from patients undergoing arthroplasty (hip replacements).

The study, published in Stem Cells this week, describes how the extracted BMMNCs were treated with the Wnt3A protein, a potent activator of the Wnt pathway. These cells were found to hold increased colony forming and osteogenic capacity when compared to untreated controls, showing the benefits of the treatment. Interestingly, sustained stimulation of the pathway by Wnt3A inhibited the osteogenesis in a concentration-dependent fashion, suggesting that although stimulation of the pathway may be appropriate for initial fracture healing, continual treatment may not be a viable option.

“Through our research, we are trying to find ways to chemically stimulate Wnt signaling using drugs. To achieve this, we selectively deliver proteins and other molecules that change Wnt signaling specifically to stem cells, particularly in the bone. This may help us find cures for many diseases, including bone disease, and speed up bone healing after fracture,” Evans concluded.

Sources: New approach to help bones heal faster and better, Press Release;
Janeczek AA, Tare RS, Scarpa E et al. Transient Canonical Wnt Stimulation Enriches Human Bone Marrow Mononuclear Cell Isolated for Osteoprogenitors. Stem Cells. DOI