Loss of cartilage stem cells drives osteoarthritis in mice

Osteoarthritis progression in mice is due to the loss of stem cells that produce cartilage in the joints, researchers have proposed.

Osteoarthritis is a painful condition characterised by the degeneration of cartilage in the joints, and is more common in older people, with the exact causes remaining unclear. The only treatment, other than symptom relief, is joint replacement, which requires surgery. It has been assumed the degeneration of cartilage that characterises the disease is caused by 'wear and tear' at the joints, but now researchers from the University of Adelaide, Australia, have suggested it could, at least partially, be caused by loss of the stem cells that produce cartilage at the joints.

'The findings of our study reimagine osteoarthritis not as a 'wear and tear' condition but as an active, and pharmaceutically reversible loss of critical articular cartilage stem cells,' said Dr Jia Ng who co-led the study published in Nature Communications.

Researchers used a mouse model of osteoarthritis to identify the presence of Gremlin1 (Grem1) gene-expressing stem cells that reside on the articular surface of the joint and generate articular cartilage. They found that the loss of these cells occurs early in osteoarthritis, leading to the development of the disease.

Researchers also looked at molecular targets for these cells and focused on fibroblast growth factor signaling. They found that treating the mice with a growth factor called FGF18 increased the proliferation of these cells, increased cartilage thickness, and decreased osteoarthritis.

Dr Ng commented 'With this new information, we are now able to explore pharmaceutical options to directly target the stem cell population that is responsible for the development of articular cartilage and progression of osteoarthritis. Our study suggests that there may be new ways to treat the disease rather than just the symptoms, leading to better health outcomes and quality of life for people who suffer from osteoarthritis.'

Reduction of blood stem cell diversity in old age has been linked to old-age health issues (see BioNews 1146).