The molecular pathway by which cartilage breaks down, causing painful osteoarthritis, is associated with an age-related decrease in the level of a protein called HMGB2, scientists have found (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0806062106). The identification of this molecular target could lead to therapeutics for osteoarthritis, which can currently be treated only with palliative drugs that reduce pain and inflammation. “We have found the mechanism that begins to explain how and why aging leads to deterioration of articular cartilage,” says arthritis researcher Martin Lotz of Scripps Research Institute, who carried out the study with Noboru Taniguchi, also of Scripps, and coworkers. The scientists found that HMGB2 is expressed in the surface layer of cartilage in human joints where it supports chondrocytes, which are the cells that produce and maintain cartilage. The study results show that aging leads to lower levels of HMGB2 and the consequent loss of chondrocytes. Preventing the loss of HMGB2-expressing chondrocytes or restoring them to a normal level could be an effective approach to ameliorate osteoarthritis, the researchers write.