These photographs show what happens when a certain protein is inactivated in the ankle joints of developing mice. Particular joints completely fail to form. Elsewhere in the body, joints do form, but they are not maintained. Both conditions are evident from the lack of blue staining in the right-hand image. The photographs appear in a paper by David M. Kingsley and colleagues (PLoS Biol. 2, e355; 2004), and the findings bear on our understanding of human osteoarthritis.

In healthy joints, where two bones meet, the ends of the bones are covered in cartilage, helping to reduce friction. In people with osteoarthritis, however, the cartilage wears away, so that the underlying bones are exposed and rub together painfully. To investigate the molecular mechanisms involved, Kingsley and colleagues built on the knowledge that certain proteins of the bone morphogenetic protein (BMP) family are involved in joint formation. Using a complex genetic system, they generated mice in which a BMP receptor, the BMPR1a protein, is selectively inactivated in the joints.

In these mice, some joints did not form at all; others did form, but the cartilage gradually wore away, producing the physical and behavioural characteristics of osteoarthritis. The authors suggest that signalling pathways activated by BMPR1a are needed to maintain the production of components of the cartilage extracellular matrix. And they propose that mutations in BMPR1a might account for some of the genetic variation that is known to contribute to human osteoarthritis.